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ISSN : 1225-0171(Print)
ISSN : 2287-545X(Online)
Korean Journal of Applied Entomology Vol.61 No.1(Special Issue) pp.15-28
DOI : https://doi.org/10.5656/KSAE.2022.02.0.013

Pheromone Biosynthesis Activating Neuropeptide (PBAN) in Insects

Man-yeon Choi*
Horticultural Crops Research Unit, USDA ARS, 3420 NW Orchard Avenue, Corvallis, OR 97330, USA
*Corresponding author:man-yeon.choi@usda.gov
January 16, 2022 February 3, 2022 February 11, 2022

Abstract


Neuropeptides produced in neurosecretory cells are the largest group of insect hormones. They regulate various physiological functions, such as fat body homeostasis, feeding, digestion, excretion, circulation, reproduction, metamorphosis, and behavior throughout all life stages. The PRXamide peptide family (X, a variable amino acid) is a well-characterized neuropeptide component with a common amino acid sequence, PRXamide (NH2), at the C-terminal end conserved across Insecta. The PRXamide peptides are classified into three subfamilies, each having diverse biological roles in insects: (1) pyrokinin (PK) includes the pheromone biosynthesis activating neuropeptide (PBAN) and the diapause hormone (DH), (2) the capability (CAPA) peptides, and (3) the ecdysis-triggering hormone (ETH). PBAN as a member of PK subfamily was first identified to stimulate pheromone biosynthesis in moths three decades ago. Since then, PBAN peptides have been extensively studied by various research groups from a broad spectrum of arthropods. In this paper, we briefly review insect PBAN molecules with emphasis on gene structure and expression, signal transduction, physiological mechanism in sex pheromone biosynthesis, and application for pest management.



곤충의 페로몬 생합성 활성화 신경펩타이드(PBAN)

최 만연*
미농무부 농업연구청

초록


신경펩타이드(Neuropeptide)는 신경세포에서 분비되는 단백질성 물질로, 곤충 호르몬에서 가장 큰 그룹으로 차지한다. 이들은 곤충의 전 생육단계에 걸쳐 지방체의 항상성, 섭식, 소화, 배설, 순환, 번식, 탈피/변태 등 다양한 생리적 기능과 행동을 조절하는데 관여하고 있다. 신경호 르몬 일종인 PRXamide (NH2) 펩타이드 계열 호르몬은 카르복실기 끝에 PRX (X, 다양한 아미노산)라는 공통의 아미노산 서열이 특징적으로 존재하고 있으며, 곤충 전반에 걸쳐 발견된다. 곤충에서PRX 신경호르몬은 다양한 생물학적 기능에 관련하고 있는데 호르몬구조와 기능에 따라 크게 3가지로 분류한다. Pyrokinin (PK)계열의 호르몬은 페로몬 생합성 활성화 신경펩타이드(pheromone biosynthesis activating neuropeptide, PBAN) 및 휴면 호르몬(diapause hormone, DH)이 속하며, 카파(CAPA) 펩타이드 호르몬, 그리고 탈피촉진 호르몬(ecdysis trigging hormone, ETH)이 여기에 속한다. PK 계열의 PBAN 호르몬은 지금으로부터 약 30년전 나방에서 처음 밝혀졌으며, 성페로몬 생합성 을 자극하는 신경호르몬으로 확인되었다. 그 이후, PBAN의 연구는 절지동물 전반에 걸쳐 다양한 연구자들에 의하여 광범위하게 이루어졌다. 본 종설은 PBAN의 유전자 구조와 발현, PBAN에 의한 세포신호 전달과 성페로몬 생합성에 관련된 생리적 기작, 그리고 신경호르몬과 PBAN을 이용한 새로운 해충 방제법 개발의 가능성과 예를 소개한다.



    PBAN is one of the neurohormones in insects. Insect neurohormones are produced in neurosecretory cells and are typically composed of neuropeptides (NPs) with < 50 amino acids and stable protein molecules. NPs occupy over 90% of total insect hormones and nearly 50 NP families from over 400 different insect species have been identified (Boo, 2001;Garczynski et al., 2019;Nassel, 2002;Nassel and Homberg, 2006;Nassel and Winther, 2002, 2010;Nassel and Zandawala, 2019;Vanden Broeck, 2001;Veenstra, 2016;Yeoh et al., 2017). NPs regulate or modulate a variety of physiological actions, such as fat body homeostasis, feeding, digestion, excretion, circulation, reproduction, metamorphosis, and behavior throughout all life stages (Altstein and Nassel, 2010;Bendena, 2010;Gade and Hoffmann, 2005;Nassel and Winther, 2010;Nassel and Zandawala, 2019;Schoofs et al., 2017).

    The PRXamide family of neuropeptides is conserved across Insecta (Jurenka, 2015), is well-characterized, and has a common amino acid sequence: PRXamide (-NH2) (X= a variable amino acid) at the C-terminal end. The PRXamide family peptides are classified into three subfamilies, each having diverse biological roles in insects: (1) pyrokinin (PK) includes the pheromone biosynthesis activating neuropeptide (PBAN) and the diapause hormone (DH) (peptides normally produced from the single pk/pban/dh gene), (2) the capability (CAPA) peptides (peptides produced from the capa gene), and (3) the ecdysis-triggering hormone (ETH) (peptides produced from the eth gene) (Ahn and Choi, 2018;Jurenka, 2015). Since the 1980s, the PK subfamily has been extensively studied by various research groups, the first peptide, leucopyrokinin, was isolated from the cockroach, Leucophaea maderae, to stimulate muscle contraction and myotropic activity in insects (Holman et al., 1986;Lajevardi and Paluzzi, 2020;Schoofs et al., 1993). Soon after then, many NPs of PK subfamily were found to stimulate pheromone biosynthesis by PBAN (Choi and Vander Meer, 2012a;Kitamura et al., 1989;Raina et al., 1989), and induce embryonic diapause by DH in the silkworm (Imai et al., 1991;Sato et al., 1993), terminate larval and pupal diapause in moths (Suang et al., 2017;Xu and Denlinger, 2003;Zhang et al., 2004), control molting and metamorphosis in the moth (Watanabe et al., 2007), modulate feeding behavior in the fly (Melcher and Pankratz, 2005), induce larval cuticular melanization in moths (Matsumoto et al., 1990;Matsumoto et al., 1992), and to accelerate fly pupariation (Zdarek et al., 1997, 1998). In this paper, we briefly review insect PBAN molecules with emphasis on gene structure and expression, signal transduction, physiological mechanism in sex pheromone biosynthesis, and application for pest management.

    Molecular Structure of PBAN

    The PK subfamily peptides are composed of two NP groups, PK1 and PK2 peptides, that are differentiated by variations in the C-terminal motif and have their own receptors for different biological signals (Choi et al., 2017;Hull et al., 2021;Jurenka and Nusawardani, 2011;Jurenka, 2015). PK1 peptides, occasionally referred to as tryptoPKs or DH-like peptides, are characterized by a WFGPRLamide C-terminus. In contrast, PK2 peptides, such as PBANs, lack the Trp (W) residue and have C-terminal ends consisting of FXPRLamide or similar motifs (X = a variable amino acid) (Hull et al., 2021). To date, over 250 PK/PBAN/DH peptides have been identified from over 50 species in various insect groups (Choi et al., 2015;Choi and Vander Meer, 2012b;Garczynski et al., 2019;Jurenka, 2015), but the biological functions of these peptides are largely unknown.

    In moths, the PK1 (= DH-like) and PK2 (= PBAN-like) peptides are usually transcribed from the same gene, called various names, pk, pban, dh, dh/pban, pk/pban/dh genes, depending on research groups. Number of mature peptides translated from these genes is estimated from one to five peptides. Most insect pk/pban/dh genes are encoding a single PK1 (WFGPRLamide) or no PK1 and multiple PK2 (FXPRLamide) peptides (Fig. 1). Lepidopteran species have been found to produce five NPs, one PK1 (= DH-like) and four PK2 (= PBAN-like) peptides including PBAN. The C-terminal pentapeptides are significant in stimulating pheromone biosynthesis in moths (Kuniyoshi et al., 1992a;Kuniyoshi et al., 1992b;Ma et al., 1996;Raina and Kempe, 1990) and binding to their receptors (Ahn et al., 2020;Kim et al., 2008). Beyond Lepidoptera, other insect groups (e.g., Hymenoptera, Coleoptera, Hemiptera, and Diptera) are expected to produce variable numbers of their mature peptides (1-4 NPs) (Ahn and Choi, 2018;Choi et al., 2015;Choi and Vander Meer, 2012b;Choi et al., 2011;Jurenka, 2015). Amino acids sequences of each mature peptide encoded from pban genes are usually estimated based on mono or dibasic cleavage sites in insect neuropeptides (Southey et al., 2008;Veenstra, 2000), or confirmed by a mass spectrometry analysis (Ma et al., 2000). However, preproPK peptides encoded from the pk/pban/dh transcripts are unclear whether their mature peptides are released or not (Choi et al., 2015). For example, the PBAN-like peptide (QPQPVFYHSTTPRLamide) of the mosquito Ades aegypti was expected to be processed as a mature peptide based on the sequence (Bader et al., 2007b), however, the peptide has not been detected from the subesophageal ganglion (SEG) by the mass spectroscopy (Predel et al., 2010). Therefore, this peptide might not be translated and released in the mosquito, but, further study is necessary to confirm the presence or absence of the mature peptide. Another case is QLQSNGEPAYRVRTPRLamide peptide of the fruit fly Drosophila melanogaster that had been proposed as a hugin prepropeptide (Meng et al., 2002), but this peptide was also never detected from the fly central nervous system (CNS) or ring gland by multiple peptidomic analyses (Baggerman et al., 2005;Baggerman et al., 2002;Wegener et al., 2006). In insects, D. melanogaster has the simplest pk/pban/dh gene, producing a single PK2 (= PBAN-like) peptide, followed by the sand fly Phlebotomus papatasi with two PK2 (= PBAN-like) peptides (Fig. 1).

    Expression and Synthesis of PBAN

    PBAN is synthesized in SEG (Raina et al., 1989), which is now referred to as the gnathal ganglia (GNG), located near the brain (Ito et al., 2014), and released into the hemolymph, where it travels to the pheromone glands to activate pheromone biosynthesis in moths (Altstein, 2004b;Jurenka, 2017;Rafaeli, 2009). In Noctuidae moths, female adults typically produce and release their sex pheromones during the scotophase only, not photophase (Choi et al., 1998b). However, expressions of pk/pban/dh transcripts and mature peptides are found in the neurosecretory cells regardless of the photoperiods. In addition, sex pheromone components can be biosynthesized in the pheromone gland, when PBAN molecules are injected into female moths during the daytime, indicating the PBAN receptor is always active (Choi and Jurenka, 2004;2006b). These results suggest that female adults will synthesize PBAN molecules all the time but not release them into hemolymph during the daytime; the endocrinal control could be under the circadian regulation for releasing PBAN into the hemolymph from the GNG (Bloch et al., 2013). Also, the pban transcripts were clearly expressed in all the developmental stages of the silkworm and corn earworm (Ma et al., 1994;Ma et al., 1998;Xu et al., 1995) and in the male and female moths (Choi et al., 1998a;Ma et al., 1998;Rafaeli et al., 2007). Expressions of pban/dh transcripts using mRNA detection methods (Choi et al., 2017;Choi et al., 2013;Choi et al., 2014;Choi et al., 2015;Choi and Vander Meer, 2012a;Choi et al., 2012;Lee and Boo, 2005;Senthilkumar and Srinivasan, 2019;Wei et al., 2004b;Xu and Denlinger, 2003) or PBAN-like peptides in CNS using immunocytochemistry and/or mass spectrometry were confirmed in various insect groups (Ahn and Choi, 2018;Chen et al., 2019;Choi et al., 2004;Choi et al., 2001;Choi and Vander Meer, 2009;Hull et al., 2021;Ma et al., 2000;Ma and Roelofs, 1995b;Sun et al., 2003;Wei et al., 2008). The ubiquitous presence of PBAN-like molecules during different life stages indicates that the role of PBAN-like could be involved in multiple biological functions such as feeding activity (Audsley and Weaver, 2009;Bader et al., 2007a;Bader et al., 2007b;Melcher et al., 2007;Melcher and Pankratz, 2005) and molting process (Watanabe et al., 2007).

    Signal Transduction of PBAN

    Since the first PBAN in a moth (Raina et al., 1989), PBAN signaling to sex pheromone biosynthesis has been well understood in various moths (Jurenka, 2017). To date, no other insect groups have been reported to regulate pheromone biosynthesis using PBAN except the fire ant trail pheromone (Choi and Vander Meer, 2012a). A general PBAN mode of action model is that PBAN is synthesized in GNG and released into the hemolymph to circulate and reach the target pheromone gland. Early immunocytochemical and physiological evidence suggested PBAN travels to the pheromone gland through humoral, neural, or both routes, which suggests that sex pheromone biosynthesis can be regulated through circulation in the hemolymph (Choi et al., 1998b;Jacquin et al., 1994;Jurenka et al., 1993;Jurenka et al., 1991a;Raina, 1993;Raina and Klun, 1984;Ramaswamy et al., 1995;Ramaswamy et al., 1994;Zhu et al., 1995), or through the ventral nerve cord (Christensen and Hildebrand, 1995;Christensen et al., 1991;Christensen et al., 1994;Iglesias et al., 1998;Marco et al., 1996;Teal et al., 1989;Teal et al., 1999b;Thyagaraja and Raina, 1994). Now, PBAN signaling through the hemolymph as a humoral route is most likely involved in pheromone production in moths.

    PBAN acts directly on pheromone glands by stimulating specific receptor linked G proteins to open a ligand-gated calcium channel to allow the influx of extracellular calcium ions (Ca2+), which is the critical second messenger for PBAN signal transduction (Fonagy et al., 1992;Jurenka, 1996;Jurenka et al., 1994;Jurenka et al., 1991b;Ma and Roelofs, 1995a;Matsumoto et al., 1995a;Matsumoto et al., 1995b;Rafaeli and Soroker, 1994). The increased cytosolic calcium ions activate the adenylate cyclase to produce cAMP, which activates various enzymes involved in sex pheromone biosynthesis (Jurenka, 2017;Rafaeli and Gileadi, 1996). In other moths, like Bombyx mori and Ostrinia nubilalis, Ca2+ ions directly activate specific enzymes involved in sex pheromone biosynthesis (Fonagy et al., 1992;Ma and Roelofs, 1995a). Once PBAN binds to the receptor, a signal coupled to G proteins is initiated that induces the opening of a plasma membrane calcium channel (Choi et al., 2003;Choi and Jurenka, 2004, 2006b;Jurenka, 2017).

    The signal transduction mechanism for enzyme activation is turned on quickly once PBAN binds with its receptor, PBAN receptor (PBAN-R), and the pathway stays activated for a period of time. It is possible that some PBAN remains bound to the receptor, and may stay activated and continuously keep the calcium channel open. In moth species, maximum pheromone production occurs about 45 min after the initial exposure to PBAN using in vivo incubations (Choi and Jurenka, 2004;Choi et al., 1998b;Gazit et al., 1990;Rafaeli and Gileadi, 1995). Therefore, the signal transduction of PBAN in the pheromone gland is initiated by PBAN binding to PBAN-R, which is the first step for the functional PBAN; it has been a longstanding question until the identification of insect PBAN-R. The first G protein-coupled receptor (GPCR) for PBAN has been identified from the pheromone glands of the corn earworm Helicoverpa zea (Choi et al., 2003), followed by the silkworm B. mori (Hull et al., 2004), and identified many GPCRs for insect PBANs (Jurenka, 2015). Identifying additional GPCRs for PK peptides (= PBAN and DH-like) is necessary to clarify the signal transduction of unknown physiological roles of these peptides in insect development beyond pheromone regulation because PK peptides could activate their receptors associated with target organs/tissues.

    Sex Pheromone Biosynthesis by PBAN

    Sex pheromone components in moths are generally linear fatty acid-derived compounds, C10–18 hydrocarbon chains, with one to three double bonds, and alcohol, acetate ester, aldehyde, or epoxide as a functional group (Choi et al., 2016;Jurenka, 2003, 2004;Tillman et al., 1999). Specific enzymes are present in the pheromone glands of female moths and are involved in key steps of the pheromone biosynthetic pathway. These enzymes include fatty acid synthetases, desaturases, limited chain-shortening enzymes, and functional modification of the carbonyl carbon to make species-specific pheromone blends (Choi et al., 2016;Choi et al., 2005;Choi et al., 2002;Choi and Jurenka, 2006a;Choi et al., 2007;Dou et al., 2019;Jurenka, 2003, 2004). Female sex pheromone glands in Heliothine moths are typically located on the intersegmental cuticle between the 8th and 9th abdominal segments just anterior to the ovipositor (Li et al., 2015;Ma and Ramaswamy, 2003;Raina et al., 2000). The biosynthesis of sex pheromones in moths, not all moth species, is regulated by PBAN, which binds to the PBAN receptor on pheromone glands to activate specific enzymes related to specific pheromone biosynthetic pathway (Jurenka, 2017;Jurenka and Rafaeli, 2011). Examples of biosynthetic pathways in Heliothne moths are shown in Fig. 2: 1) biosynthesize saturated fatty acids as sex pheromone precursors; 2) introduce double bonds by fatty acyl-CoA desaturases into the fatty acyl chains; 3) occur one or two rounds of chain shortening steps by limited β-oxidation enzymes; 4) modify functional groups by oxidases, reductases, or acetyltransferases (Blomquist and Vogt, 2020;Choi et al., 2002;Jurenka, 2004).

    For the biosynthesis of the hydrocarbon moth pheromones, the PBAN action is different in that acts in the final biosynthetic step. In the gypsy moth Lymantria dispar, as a case study, PBAN is involved in the final step which is the enzyme epoxidation process in the pheromone gland (Jurenka, 2003). Most pheromone biosynthetic steps occur in the oenocyte cells associated with the abdominal epidermis. After the hydrocarbon pheromone precursor is biosynthesized in oenocyte cells, it is then transported to the pheromone gland through hemolymph by lipophorin. The alkene precursor is taken up by pheromone gland cells, where it is acted on by an epoxidase to produce the sex pheromone, disparlure; PBAN activates the epoxidation enzyme in the gypsy moth pheromone gland (Jurenka et al., 2003;Miyamoto et al., 1999;Wei et al., 2003;Wei et al., 2004a).

    Applications for Pest Management

    Over two decades, the PRXamide peptides/receptors have been considered promising targets for pest control, because they are involved in various key biological processes described above (Altstein, 2001, 2004b; Altstein et al., 2000;Altstein and Nassel, 2010;Audsley and Down, 2015;Caers et al., 2012;Gade and Goldsworthy, 2003;Liu et al., 2021;Masler et al., 1993;Nachman et al., 1993;Pietrantonio et al., 2018;Scherkenbeck and Zdobinsky, 2009;Van Hiel et al., 2010). Disruption of an essential function(s) of PK/PBAN/DH peptides leads to novel pest management. In early years, although there were significant efforts to utilize insect NPs/GPCRs as insecticides, little progress was made. New genomic and proteomic technology and tools have advanced and facilitated the development of new approaches to insecticide discovery (Du et al., 2017;Fleites et al., 2020;Grimmelikhuijzen et al., 2007). Currently, three biological tools using the PRXamide peptides and their GPCRs are under development. First, the most popular and conventional approach by peptide biochemists uses NP analogs and mimics to identify biological functions in insects (Nachman et al., 1986). Recently, many peptide mimics and analogs as agonists (PBAN-R activators) or antagonists (PBAN-R inhibitors) have been isolated or identified from a broad spectrum of arthropod pests (Abernathy et al., 1996;Alford et al., 2019;Altstein, 2004a;Altstein et al., 1999;Altstein et al., 2007;Ben-Aziz et al., 2005;Ben-Aziz et al., 2006;Gui et al., 2020;Hariton et al., 2010;Hariton et al., 2009a;Hariton et al., 2009b;Marciniak et al., 2011;Nachman et al., 2009a;Nachman et al., 2009b;Nachman et al., 2009c;Nachman et al., 1996;Nachman et al., 2001;Nachman et al., 2009d;Plech et al., 2004;Raina et al., 1994;Shi et al., 2021;Teal et al., 1999a;Teal and Nachman, 1997;Xiong et al., 2021;Zeltser et al., 2001;Zeltser et al., 2000;Zhang et al., 2009;Zhang et al., 2011;Zubrzak et al., 2007). Various structural modifications of PK/PBAN/DH peptides, such as backbone cyclization, enable to increase hydrophobicity and stability from the natural peptide ligands and delivery into insects.

    Second, genes of the PBAN-like peptides and their GPCRs from insect pests were selected as RNA interference (RNAi) target. A handful of reports for the RNAi application have been demonstrated from a few insect pests (Choi and Vander Meer, 2012a, 2019;Choi et al., 2012;Lee et al., 2011;Lu et al., 2015;Ohnishi et al., 2006). For example, PBAN RNAi decreased sex pheromone production, increased larval mortality or delayed pupal development in the moths and ant by injection of the PBAN dsRNA (double-stranded RNA) (Choi et al., 2012;Lee et al., 2011;Lu et al., 2015).

    Lastly and most recently, PK/PBAN/DH GPCR-based agonists and antagonists have been isolated to develop pest control methods that is the newest approach (Ahn et al., 2020;Choi and Vander Meer, 2021;Jiang et al., 2015;Jiang et al., 2014). This development of new methods is available with advanced genomic/proteomic tools. The fundamental mechanism of these strategies is to screen active peptides or analogs that strongly bind to the target receptor, thus blocking the specific physiological function triggered by the natural NP and GPCR binding. Recently, GPCR-based screening technology for the isolation and identification of bioactive peptides using an insect cell expression system has been demonstrated for insecticide discovery (Choi and Vander Meer, 2021). This mode of action is called as Receptor interference (RECEPTORi). This new technology can rapidly screen bioactive peptides through millions of short peptides for blocking a specific insect GPCR system. These short peptides are not like natural ligands, but they can function as agonists or antagonists to the target GPCR.

    Conclusions

    PK/PBAN/DH family peptides and their GPCRs are found across Insecta and other invertebrates and are involved in various important biological processes during all developmental stages and in adults. With research continuing through the last three decades, these neuropeptides have been well characterized, and this research has been an integral part in understanding how their signals function and modulate a broad spectrum of physiological activities including pheromone biosynthesis and diapause in insects. The manipulation of insect neuropeptides to control pest population has great potential to be developed as target-specific, and biologically based tool in next-generation pest management.

    Acknowledgments

    The author dedicates this paper to the late Professor Kyung Saeng Boo, his forever supervisor, who initiated this project on the PBAN in sex pheromone biosynthesis three decades ago. He thanks Bri Price and Hojung Yoon for reading and editing an early version.

    KSAE-61-1-15_F1.gif

    Comparison of PK1 (= DH-like) and PK2 (= PBAN-like) neuropeptides encoded from selected pk/pban genes in Insecta. Proposed NP sequences shaded in mosquitoes and flies are not expected to be functional peptides. Full amino acid sequence comparisons are from lepidopteran species, Helicoverpa zea (U08109), Helicoverpa assulta (U96761), Helicoverpa armigera (AY043222), Heliothis virescens (AY173075), Agrotisi psilon (AJ009674), Spodoptera littoralis (AF401480), Spodoptera exigua (AY628764), Clostera anastomosis (AY786305), Orgyia thyellina (AB259122), Antheraea pernyi (AY445658), Bombyx mori (NM_001043856), B. mandarina (Xu et al., 1999), Manduca sexta (AY172672), Samia cynthia ricini (AY286544), Adoxophyes sp. (AF395670), Cydia pomonella (QDK59915), Plutella xylostella (AY904342), Ascotis selenaria cretacea (AB308061), Maruca vitrata (AFX71575), Danaus plexippus (EHJ67284); hymenopteran species, Solenopsis invicta (ACL35348), Solenopsis richteri (ADI88481), Solenopsis geminate (ADI88478), Solenopsis pergandei (ADI88479), Solenopsis carolinensis (ADI88480), Apis melifera (NP_001104182); coleopteran species, Tribolium castaneum (EFA11568); hemipteran species, Bemisia tabaci (XP_018895833), Aphis glycines (KAE9544772), Acyrthosiphon pisum (XP_003245653), Halyomorpha halys (XP_014289936); and dipteran species, Anopheles gambiae (XM_307885), Aedes aegypti (Q16N80), Phlebotomus papatasi (AIY99907), Drosophila melnogaster (AAF54833). Genebank accession numbers are in parenthesis (updated from Choi et al., 2015).

    KSAE-61-1-15_F2.gif

    Biosynthetic pathways of sex pheromone components produced by females of the corn earworm, Helicoverpa zea and the oriental tobacco budworm, Helicoverpa assulta. The major pathways are indicated with thick arrows. Hexadecanoic acid (16:Acid), Octadecanoic acid (18:Acid), (Z)-7-hexdecanoic acid (Z7-16:Acid), (Z)-9-hexadecanoic acid (Z9-16:Acid), (Z)-11-hexadecanoic acid (Z11-16:Acid), (Z)-9-octadecanoic acid (Z9-18:Acid), (Z)-11-octadecanoic acid (Z11-18:Acid), (Z)-7-hexdecenal (Z7-16:Ald), (Z)-9-hexadecenal (Z9-16:Ald), (Z)-11-hexadecenal (Z11-16:Ald), Δ11=Δ11 desaturase, Δ9=Δ9 desaturase (modified from Choi et al., 2002).

    Reference

    1. Abernathy, R.L. , Teal, P.E. , Meredith, J.A. , Nachman, R.J. ,1996. Induction of pheromone production in a moth by topical application of a pseudopeptide mimic of a pheromonotropic neuropeptide. Proc. Natl. Acad. Sci. U. S. A. 93, 12621-12625.
    2. Ahn, S.J. , Choi, M.Y. ,2018. Identification and characterization of capa and pyrokinin genes in the brown marmorated stink bug, Halyomorpha halys (Hemiptera): Gene structure, immunocytochemistry, and differential expression. Arch. Insect Biochem. Physiol. 99, e21500.
    3. Ahn, S.J. , Mc Donnell, R.J. , Corcoran, J.A. , Martin, R.C. , Choi, M.Y. ,2020. Identification and functional characterization of the first molluscan neuromedin U receptor in the slug, Deroceras reticulatum. Sci. Rep. 10, 22308.
    4. Alford, L. , Marley, R. , Dornan, A. , Pierre, J.S. , Dow, J.A. , Nachman, R.J. , Davies, S.A. ,2019. Assessment of neuropeptide binding sites and the impact of biostable kinin and CAP2b analogue treatment on aphid (Myzus persicae and Macrosiphum rosae) stress tolerance. Pest. Manag. Sci. 75, 1750-1759.
    5. Altstein, M. ,2001. Insect neuropeptide antagonists. Biopolymers 60, 460-473.
    6. Altstein, M. ,2004a. Novel insect control agents based on neuropeptide antagonists: The PK/PBAN family as a case study. J. Mol. Neurosci. 22, 147-157.
    7. Altstein, M. ,2004b. Role of neuropeptides in sex pheromone production in moths. Peptides 25, 1491-1501.
    8. Altstein, M. , Ben-Aziz, O. , Daniel, S. , Schefler, I. , Zeltser, I. , Gilon, C. ,1999. Backbone cyclic peptide antagonists, derived from the insect pheromone biosynthesis activating neuropeptide, inhibit sex pheromone biosynthesis in moths. J. Biol. Chem. 274, 17573- 17579.
    9. Altstein, M. , Ben-Aziz, O. , Schefer, I. , Zeltser, I. , Gilon, C. ,2000. Advances in the application of neuropeptides in insect control. Crop. Protection. 19, 547-555.
    10. Altstein, M. , Ben-Aziz, O. , Zeltser, I. , Bhargava, K. , Davidovitch, M. , Strey, A. , Pryor, N. , Nachman, R.J. ,2007. Inhibition of PK/PBAN-mediated functions in insects: discovery of selective and non-selective inhibitors. Peptides 28, 574-584.
    11. Altstein, M. , Nassel, D.R. ,2010. Neuropeptide signaling in insects, in: Geary, T.G., Maule, A.G. (Eds.), Neuropeptide Systems as Targets for Parasite and Pest Control. Springer, New York, pp. 155-165.
    12. Audsley, N. , Down, R.E. ,2015. G protein coupled receptors as targets for next generation pesticides. Insect Biochem. Mol. Biol. 67, 27-37.
    13. Audsley, N. , Weaver, R.J. ,2009. Neuropeptides associated with the regulation of feeding in insects. Gen. Comp. Endocrinol. 162, 93-104.
    14. Bader, R. , Colomb, J. , Pankratz, B. , Schrock, A. , Stocker, R.F. , Pankratz, M.J. ,2007a. Genetic dissection of neural circuit anatomy underlying feeding behavior in Drosophila: distinct classes of hugin-expressing neurons. J. Comp. Neurol. 502, 848-856.
    15. Bader, R. , Wegener, C. , Pankratz, M.J. ,2007b. Comparative neuroanatomy and genomics of hugin and pheromone biosynthesis activating neuropeptide (PBAN). Fly 1, 228-231.
    16. Baggerman, G. , Boonen, K. , Verleyen, P. , De Loof, A. , Schoofs, L. ,2005. Peptidomic analysis of the larval Drosophila melanogaster central nervous system by two-dimensional capillary liquid chromatography quadrupole time-of-flight mass spectrometry. J. Mass. Spectrom. 40, 250-260.
    17. Baggerman, G. , Cerstiaens, A. , De Loof, A. , Schoofs, L. ,2002. Peptidomics of the larval Drosophila melanogaster central nervous system. J. Biol. Chem. 277, 40368-40374.
    18. Ben-Aziz, O. , Zeltser, I. , Altstein, M. ,2005. PBAN selective antagonists: inhibition of PBAN induced cuticular melanization and sex pheromone biosynthesis in moths. J. Insect Physiol. 51, 305- 314.
    19. Ben-Aziz, O. , Zeltser, I. , Bhargava, K. , Davidovitch, M. , Altstein, M. ,2006. Backbone cyclic pheromone biosynthesis activating neuropeptide (PBAN) antagonists: inhibition of melanization in the moth Spodoptera littoralis (Insecta, Lepidoptera). Peptides 27, 2147-2156.
    20. Bendena, W.G. ,2010. Neuropeptide Physiology in Insects, in: Geary, T.G., Maule, A.G. (Eds.), Neuropeptide Systems as Targets for Parasite and Pest Control. Springer, New York, pp. 166-191.
    21. Bloch, G. , Hazan, E. , Rafaeli, A. ,2013. Circadian rhythms and endocrine functions in adult insects. J. Insect Physiol. 59, 56-69.
    22. Blomquist, G.J. , Vogt, R.G. ,2020. Insect pheromone biochemistry and molecular biology, 2 ed. Elsevier, Cambridge.
    23. Boo, K.S. ,2001. Insect hormones and their actions. Korean J. Appl. Entomol 40, 155-196.
    24. Caers, J. , Verlinden, H. , Zels, S. , Vandersmissen, H.P. , Vuerinckx, K. , Schoofs, L. ,2012. More than two decades of research on insect neuropeptide GPCRs: an overview. Front. Endocrinol. (Lausanne) 3, 151.
    25. Chen, Y. , Liu, Y. , Tian, H. , Chen, Y. , Lin, S. , Mao, Q. , Zheng, N. , Zhao, J. , Gu, X. , Wei, H. ,2019. Distribution of pheromone biosynthesis- activating neuropeptide in the central nervous system of Plutella xylostella (Lepidoptera: Plutellidae). J. Econ. Entomol. 112, 2638-2648.
    26. Choi, M.Y. , Ahn, S.J. , Kim, A.Y. , Koh, Y. ,2017. Identification and characterization of pyrokinin and CAPA peptides, and corresponding GPCRs from spotted wing drosophila, Drosophila suzukii. Gen. Comp. Endocrinol. 246, 354-362.
    27. Choi, M.Y. , Ahn, S.J. , Park, K.C. , Vander Meer, R. , Carde, R.T. , Jurenka, R.A. ,2016. Tarsi of male Heliothine moths contain aldehydes and butyrate esters as potential pheromone components. J. Chem. Ecol. 42, 425-432.
    28. Choi, M.Y. , Estep, A. , Sanscrainte, N. , Becnel, J. , Vander Meer, R.K. ,2013. Identification and expression of PBAN/diapause hormone and GPCRs from Aedes aegypti. Mol. Cell. Endocrinol. 375, 113-120.
    29. Choi, M.Y. , Fuerst, E.J. , Rafaeli, A. , Jurenka, R.A. ,2003. Identification of a G protein-coupled receptor for pheromone biosynthesis activating neuropeptide from pheromone glands of the moth Helicoverpa zea. Proc. Natl. Acad. Sci. U. S. A. 100, 9721-9726.
    30. Choi, M.Y. , Groot, A. , Jurenka, R.A. ,2005. Pheromone biosynthetic pathways in the moths Heliothis subflexa and Heliothis virescens. Arch. Insect Biochem. Physiol. 59, 53-58.
    31. Choi, M.Y. , Han, K.S. , Boo, K.S. , Jurenka, R.A. ,2002. Pheromone biosynthetic pathways in the moths Helicoverpa zea and Helicoverpa assulta. Insect Biochem. Mol. Biol. 32, 1353-1359.
    32. Choi, M.Y. , Jurenka, R.A. ,2004. PBAN stimulation of pheromone biosynthesis by inducing calcium influx in pheromone glands of Helicoverpa zea. J. Insect Physiol. 50, 555-560.
    33. Choi, M.Y. , Jurenka, R.A. ,2006a. C75, a fatty acid synthase inhibitor, inhibits feeding activity and pheromone production in a moth, Helicoverpa zea. J. Asia Pac. Entomol. 9, 43-48.
    34. Choi, M.Y. , Jurenka, R.A. ,2006b. Role of extracellular Ca2+ and calcium channel activated by a G protein-coupled receptor regulating pheromone production in Helicoverpa zea (Lepidoptera: Noctuidae). Ann. Entomol. Soc. Am. 99, 905-909.
    35. Choi, M.Y. , Kohler, R. , Vander Meer, R.K. , Neupert, S. , Predel, R. ,2014. Identification and expression of capa gene in the fire ant, Solenopsis invicta. PLoS ONE 9, e94274.
    36. Choi, M.Y. , Lee, J.M. , Han, K.S. , Boo, K.S. ,2004. Identification of a new member of PBAN family and immunoreactivity in the central nervous system from Adoxophyes sp. (Lepidoptera: Tortricidae). Insect Biochem. Mol. Biol. 34, 927-935.
    37. Choi, M.Y. , Lim, H. , Park, K.C. , Adlof, R. , Wang, S. , Zhang, A. , Jurenka, R.A. ,2007. Identification and biosynthetic studies of the hydrocarbon sex pheromone in Utetheisa ornatrix. J. Chem. Ecol. 33, 1336-1345.
    38. Choi, M.Y. , Rafaeli, A. , Jurenka, R.A. ,2001. Pyrokinin/PBANlike peptides in the central nervous system of Drosophila melanogaster. Cell Tissue Res. 306, 459-465.
    39. Choi, M.Y. , Sanscrainte, N.D. , Estep, A.S. , Vander Meer, R.K. , Becnel, J.J. ,2015. Identification and expression of a new member of the pyrokinin/pban gene family in the sand fly Phlebotomus papatasi. J. Insect Physiol. 79, 55-62.
    40. Choi, M.Y. , Tanaka, M. , Kataoka, H. , Boo, K.S. , Tatsuki, S. ,1998a. Isolation and identification of the cDNA encoding the pheromone biosynthesis activating neuropeptide and additional neuropeptides in the oriental tobacco budworm, Helicoverpa assulta (Lepidoptera: Noctuidae). Insect Biochem. Mol. Biol. 28, 759-766.
    41. Choi, M.Y. , Tatsuki, S. , Boo, K.S. ,1998b. Regulation of sex pheromone biosynthesis in the oriental tobacco budworm, Helicoverpa assulta (Lepidoptera: Noctuidae). J. Insect Physiol. 44, 653-658.
    42. Choi, M.Y. , Vander Meer, R.K. ,2009. Identification of a new member of the PBAN family of neuropeptides from the fire ant, Solenopsis invicta. Insect Mol. Biol. 18, 161-169.
    43. Choi, M.Y. , Vander Meer, R.K. ,2012a. Ant trail pheromone biosynthesis is triggered by a neuropeptide hormone. PLoS ONE 7, e50400.
    44. Choi, M.Y. , Vander Meer, R.K. ,2012b. Molecular structure and diversity of PBAN/pyrokinin family peptides in ants. Front. Endocrinol. (Lausanne) 3, 32.
    45. Choi, M.Y. , Vander Meer, R.K. ,2019. Phenotypic effects of PBAN RNAi using oral delivery of dsRNA to corn earworm (Lepidoptera: Noctuidae) and tobacco budworm larvae. J. Econ. Ent. 112, 434-439.
    46. Choi, M.Y. , Vander Meer, R.K. ,2021. GPCR-based bioactive peptide screening using phage-displayed peptides and an insect cell system for insecticide discovery. Biomolecules 11.
    47. Choi, M.Y. , Vander Meer, R.K. , Coy, M. , Scharf, M.E. ,2012. Phenotypic impacts of PBAN RNA interference in an ant, Solenopsis invicta, and a moth, Helicoverpa zea. J. Insect. Physiol. 58, 1159-1165.
    48. Choi, M.Y. , Vander Meer, R.K. , Shoemaker, D. , Valles, S.M. ,2011. PBAN gene architecture and expression in the fire ant, Solenopsis invicta. J. Insect Physiol. 57, 161-165.
    49. Christensen, T.A. , Hildebrand, J.G. ,1995. Neural regulation of sex pheromone glands in Lepidoptera. Invert. Neurosci. 1, 97-103.
    50. Christensen, T.A. , Itagaki, H. , Teal, P.E. , Jasensky, R.D. , Tumlinson, J.H. , Hildebrand, J.G. ,1991. Innervation and neural regulation of the sex pheromone gland in female Heliothis moths. Proc. Natl. Acad. Sci. U. S. A. 88, 4971-4975.
    51. Christensen, T.A. , Lashbrook, J.M. , Hildebrand, J.G. ,1994. Neural activation of the sex-pheromone gland in the moth Manduca sexta: real-time measurement of pheromone release. Physiological Entomology 19, 265-270.
    52. Dou, X. , Liu, S. , Ahn, S.J. , Choi, M.Y. , Jurenka, R.A. ,2019. Transcriptional comparison between pheromone gland-ovipositor and tarsi in the corn earworm moth Helicoverpa zea. Comp. Biochem. Physiol. Part D Genomics Proteomics 31, 100604.
    53. Du, M. , Zhao, W. , Jurenka, R. , Liu, X. , Yin, X. , Song, Q. , An, S. ,2017. Transcriptome analysis of Helicoverpa armigera male hairpencils: Alcohol biosynthesis and requirement for mating success. Insect Biochem. Mol. Biol. 87, 154-164.
    54. Fleites, L.A. , Johnson, R. , Kruse, A.R. , Nachman, R.J. , Hall, D.G. , MacCoss, M. , Heck, M.L. ,2020. Peptidomics approaches for the identification of bioactive molecules from Diaphorina citri. J. Proteome. Res. 19, 1392-1408.
    55. Fonagy, A. , Matsumoto, S. , Uchhiumi, K. , Mitsui, T. ,1992. Role of calcium ion and cyclic nucleotides in pheromone production in Bombyx mori. J. Pesticide. Science. 17, 115–121.
    56. Gade, G. , Goldsworthy, G.J. ,2003. Insect peptide hormones: a selective review of their physiology and potential application for pest control. Pest. Manag. Sci. 59, 1063-1075.
    57. Gade, G. , Hoffmann, K.H. ,2005. Neuropeptides regulating development and reproduction in insects. Physiol. Entomol. 30, 103- 121.
    58. Garczynski, S.F. , Hendrickson, C.A. , Harper, A. , Unruh, T.R. , Dhingra, A. , Ahn, S.J. , Choi, M.Y. ,2019. Neuropeptides and peptide hormones identified in codling moth, Cydia pomonella (Lepidoptera: Tortricidae). Arch. Insect. Biochem. Physiol. 101, e21587.
    59. Gazit, Y. , Dunkelblum, E. , Benichis, M. , Altstein, M. ,1990. Effect of synthetic PBAN and derived peptides on sex pheromone biosynthesis in Heliothis peltigera (Lepidoptera: Noctuidae). Insect Biochem. 20, 853-858.
    60. Grimmelikhuijzen, C.J. , Cazzamali, G. , Williamson, M. , Hauser, F. ,2007. The promise of insect genomics. Pest Manag. Sci. 63, 413-416.
    61. Gui, S.H. , Taning, C.N. , De Schutter, K. , Yang, Q. , Chen, P. , Hamshou, M. , Nachman, R.J. , Pandit, A.A. , Dow, J.A. , Davies, S. , Smagghe, G. ,2020. Assessment of insecticidal effects and selectivity of CAPA-PK peptide analogues against the peach-potato aphid and four beneficial insects following topical exposure. Pest Manag. Sci. 76, 3451-3458.
    62. Hariton, A. , Ben-Aziz, O. , Davidovitch, M. , Altstein, M. ,2010. Bioavailability of backbone cyclic PK/PBAN neuropeptide antagonists-- inhibition of sex pheromone biosynthesis elicited by the natural mechanism in Heliothis peltigera females. FEBS J. 277, 1035-1044.
    63. Hariton, A. , Ben-Aziz, O. , Davidovitch, M. , Nachman, R.J. , Altstein, M. ,2009a. Bioavailability of insect neuropeptides: the PK/PBAN family as a case study. Peptides 30, 1034-1041.
    64. Hariton, A. , Ben-Aziz, O. , Davidovitch, M. , Zubrzak, P. , Nachman, R.J. , Altstein, M. ,2009b. Bioavailability of beta-amino acid and C-terminally derived PK/PBAN analogs. Peptides 30, 2174-2181.
    65. Holman, G.M. , Cook, B.J. , Nachman, R.J. ,1986. Isolation, primary structure and synthesis of a blocked neuropeptide isolated from the cockroach, Leucophaea maderae. Comp. Biochem. Physiol. 85C, 219-224.
    66. Hull, J.J. , Brent, C.S. , Choi, M.Y. , Miko, Z. , Fodor, J. , Fonagy, A. ,2021. Molecular and functional characterization of Pyrokininlike peptides in the western tarnished plant bug Lygus Hesperus (Hemiptera: Miridae). Insects 12.
    67. Hull, J.J. , Ohnishi, A. , Moto, K. , Kawasaki, Y. , Kurata, R. , Suzuki, M.G. , Matsumoto, S. ,2004. Cloning and characterization of the pheromone biosynthesis activating neuropeptide receptor from the silkmoth, Bombyx mori. Significance of the carboxyl terminus in receptor internalization. J. Biol. Chem. 279, 51500-51507.
    68. Iglesias, F. , Marco, M.P. , Jacquin Joly, E. , Camps, F. , Fabrias, G. ,1998. Regulation of sex pheromone biosynthesis in two noctuid species, S. littoralis and M. brassicae, may involve both PBAN and the ventral nerve cord. Arch. Insect. Biochem. Physiol. 37, 295- 304.
    69. Imai, K. , Konno, T. , Nakazawa, Y. , Komiya, T. , Isobe, M. , Koga, K. , Goto, T. , Yaginuma, T. , Sakakibara, K. , Hasegawa, K. , Yamashita,1991. Isolation and structure of diapause hormone of the silkworm, Bombyx mori. Proc. Japan Acad. 67(B), 98-101.
    70. Ito, K. , Shinomiya, K. , Ito, M. , Armstrong, J.D. , Boyan, G. , Hartenstein, V. , Harzsch, S. , Heisenberg, M. , Homberg, U. , Jenett, A. , Keshishian, H. , Restifo, L.L. , Rossler, W. , Simpson, J.H. , Strausfeld, N.J. , Strauss, R. , Vosshall, L.B. , Insect Brain Name Working, G. ,2014. A systematic nomenclature for the insect brain. Neuron 81, 755-765.
    71. Jacquin, E. , Jurenka, R.A. , Ljungberg, H. , Nagnan, P. , Lofstedt, C. , Descoins, C. , Roelofs, W.L. ,1994. Control of sex-pheromone biosynthesis in the moth Mamestra brassicae by the pheromone biosynthesis activating neuropeptide. Insect Biochem. Mol. Biol. 24, 203-211.
    72. Jiang, H. , Wei, Z. , Nachman, R.J. , Kaczmarek, K. , Zabrocki, J. , Park, Y. ,2015. Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identification of agonists and antagonists. Peptides 68, 246-252.
    73. Jiang, H. , Wei, Z. , Nachman, R.J. , Park, Y. ,2014. Molecular cloning and functional characterization of the diapause hormone receptor in the corn earworm Helicoverpa zea. Peptides 53, 243-249.
    74. Jurenka, R. , Nusawardani, T. ,2011. The pyrokinin/ pheromone biosynthesis-activating neuropeptide (PBAN) family of peptides and their receptors in Insecta: evolutionary trace indicates potential receptor ligand-binding domains. Insect Mol. Biol. 20, 323-334.
    75. Jurenka, R.A. ,1996. Signal transduction in the stimulation of sex pheromone biosynthesis in moths. Arch. Insect Biochem. Physiol. 33, 245-258.
    76. Jurenka, R.A. ,2003. Biochemistry of female moth sex pheromones, in: Blomquist, G., Vogt, R. (Eds.), Insect Pheromone Biochemistry and Molecular Biology. Academic Press, New York, pp. 53-80.
    77. Jurenka, R.A. ,2004. Insect Pheromone Biosynthesis, in: Schulz, S. (Ed.), Topics in Current Chemistry. Springer, Berlin, pp. 97-239.
    78. Jurenka, R.A. ,2015. The PRXamide neuropeptide signalling system: Conserved in animals, in: Jurenka, R.A. (Ed.), Advances in Insect Physiology. Elsevier, pp. 123-170.
    79. Jurenka, R.A. ,2017. Regulation of pheromone biosynthesis in moths. Curr. Opin. Insect Sci. 24, 29-35.
    80. Jurenka, R.A. , Fabrias, G. , DeVoe, L. , Roelofs, W.L. ,1994. Action of PBAN and related peptides on pheromone biosynthesis in isolated pheromone glands of the redbanded leafroller moth, Argyrotaenia velutinana. Comp. Biochem. Physiol. Pharmacol. Toxicol. Endocrinol. 108, 153-160.
    81. Jurenka, R.A. , Fabrias, G. , Ramaswamy, S. , Roelofs, W.L. ,1993. Control of pheromone biosynthesis in mated redbanded leafroller moths. Arch. Insect. Biochem. Physiol. 24, 129-137.
    82. Jurenka, R.A. , Fabrias, G. , Roelofs, W.L. ,1991a. Hormonal control of female sex pheromone biosynthesis in the redbanded leafroller moth, Argyrotaenia velutinana. Insect Biochem. 21, 81-89.
    83. Jurenka, R.A. , Jacquin, E. , Roelofs, W.L. ,1991b. Stimulation of pheromone biosynthesis in the moth Helicoverpa zea: action of a brain hormone on pheromone glands involves Ca2+ and cAMP as second messengers. Proc. Natl. Acad. Sci. U. S. A. 88, 8621-8625.
    84. Jurenka, R.A. , Rafaeli, A. ,2011. Regulatory role of PBAN in sex pheromone biosynthesis of Heliothine moths. Front. Endocrinol. (Lausanne) 2, 46.
    85. Jurenka, R.A. , Subchev, M. , Abad, J.L. , Choi, M.Y. , Fabrias, G. ,2003. Sex pheromone biosynthetic pathway for disparlure in the gypsy moth, Lymantria dispar. Proc. Natl. Acad. Sci. U. S. A. 100, 809-814.
    86. Kim, Y.J. , Nachman, R.J. , Aimanova, K. , Gill, S. , Adams, M.E. ,2008. The pheromone biosynthesis activating neuropeptide (PBAN) receptor of Heliothis virescens: identification, functional expression, and structure-activity relationships of ligand analogs. Peptides 29, 268-275.
    87. Kitamura, A. , Nagasawa, H. , Kataoka, H. , Inoue, T. , Matsumoto, S. , Ando, T. , Suzuki, A. ,1989. Amino acid sequence of pheromone biosynthesis activating neuropeptide (PBAN) of the silkworm, Bombyx mori. Biochem. Biophys. Res. Commun. 163, 520-526.
    88. Kuniyoshi, H. , Nagasawa, H. , Ando, T. , Suzuki, A. ,1992a. N-terminal modified analogs of C-terminal fragments of PBAN with pheromonotropic activity. Insect Biochem. Mol. Biol. 22, 399-403.
    89. Kuniyoshi, H. , Nagasawa, H. , Ando, T. , Suzuki, A. , Nachman, R.J. , Holman, G.M. ,1992b. Cross-activity between pheromone biosynthesis activating neuropeptide (PBAN) and myotropic pyrokinin insect peptides. Biosci. Biotechnol. Biochem. 56, 167- 168.
    90. Lajevardi, A. , Paluzzi, J.V. ,2020. Receptor characterization and functional activity of pyrokinins on the hindgut in the adult mosquito, Aedes aegypti. Front. Physiol. 11, 490.
    91. Lee, D.W. , Boo, K.S. ,2005. Molecular characterization of pheromone biosynthesis activating neuropeptide from the diamondback moth, Plutella xylostella (L.). Peptides 26, 2404-2411.
    92. Lee, D.W. , Shrestha, S. , Kim, A.Y. , Park, S.J. , Yang, C.Y. , Kim, Y. , Koh, Y.H. ,2011. RNA interference of pheromone biosynthesis- activating neuropeptide receptor suppresses mating behavior by inhibiting sex pheromone production in Plutella xylostella (L.). Insect Biochem. Mol. Biol. 41, 236-243.
    93. Li, Z.Q. , Zhang, S. , Luo, J.Y. , Wang, C.Y. , Lv, L.M. , Dong, S.L. , Cui, J.J. ,2015. Transcriptome comparison of the sex pheromone glands from two sibling Helicoverpa species with opposite sex pheromone components. Sci. Rep. 5, 9324.
    94. Liu, N. , Li, T. , Wang, Y. , Liu, S. ,2021. G-protein coupled receptors (GPCRs) in insects-A potential target for new insecticide development. Molecules 26.
    95. Lu, Q. , Huang, L.Y. , Chen, P. , Yu, J.F. , Xu, J. , Deng, J.Y. , Ye, H. ,2015. Identification and RNA Interference of the pheromone biosynthesis activating neuropeptide (PBAN) in the common cutworm moth Spodoptera litura (Lepidoptera: Noctuidae). J. Econ. Entomol. 108, 1344-1353.
    96. Ma, P.W. , Garden, R.W. , Niermann, J.T. , M, O.C. , Sweedler, J.V. , Roelofs, W.L. ,2000. Characterizing the Hez-PBAN gene products in neuronal clusters with immunocytochemistry and MALDI MS. J. Insect Physiol. 46, 221-230.
    97. Ma, P.W. , Knipple, D.C. , Roelofs, W.L. ,1994. Structural organization of the Helicoverpa zea gene encoding the precursor protein for pheromone biosynthesis activating neuropeptide and other neuropeptides. Proc. Natl. Acad. Sci. U. S. A. 91, 6506-6510.
    98. Ma, P.W.K. , Knipple, D.C. , Roelofs, W.L. ,1998. Expression of a gene that encodes pheromone biosynthesis activating neuropeptide in the central nervous system of corn earworm, Helicoverpa zea. Insect Biochem. Mol. Biol. 28, 373-385.
    99. Ma, P.W.K. , Ramaswamy, S. ,2003. Biology and ultrastructure of sex pheromone producing tissue, in: Blomquist, G., Vogt, R. (Eds.), Pheromone biochemistry and molecular biology. Elsevier, London, pp. 19-51.
    100. Ma, P.W.K. , Roelofs, W.L. ,1995a. Calcium involvement in the stimulation of sex pheromone production by PBAN in the European corn borer, Ostrinia nubilalis (Lepidoptera: Pyralidae). Insect Biochem. Mol. Biol. 25, 467-473.
    101. Ma, P.W.K. , Roelofs, W.L. ,1995b. Sites of synthesis and release of PBAN-like factor in the female European corn borer, Ostrinia nubilalis. J. Insect Physiol. 41, 339-350.
    102. Ma, P.W.K. , Roelofs, W.L. , Jurenka, R.A. ,1996. Characterization of PBAN and PBAN-encoding gene neuropeptides in the central nervous system of corn earworm moth, Helicoverpa zea. J. Insect Physiol. 42, 257-266.
    103. Marciniak, P. , Pacholska-Bogalska, J. , Szymczak, M. , Rosinski, G. ,2011. Molecular and physiological characterization of the pyrokinin insect neuropeptide family. Postepy Biochem. 57, 365-371.
    104. Marco, M.P. , Fabrias, G. , Lazaro, G. , Camps, F. ,1996. Evidence for both humoral and neural regulation of sex pheromone biosynthesis in Spodoptera littoralis. Arch. Insect. Biochem. Physiol. 31, 157-167.
    105. Masler, E.P. , Kelly, T.J. , Menn, J.J. ,1993. Insect neuropeptides: discovery and application in insect management. Arch. Insect. Biochem. Physiol. 22, 87-111.
    106. Matsumoto, S. , Kitamura, A. , Nagasawa, H. , Kataoka, H. , Orikasa, C. , Mitsui, T. , Suzuki, A. ,1990. Functional diversity of a neurohormone produced by the suboesophageal ganglion: Molecular identity of melanization and reddish colouration hormone and pheromone biosynthesis activating neuropeptide. J. Insect Physiol. 36, 427-432.
    107. Matsumoto, S. , Ozawa, R. , Nagamine, T. , Kim, G.H. , Uchiumi, K. , Shono, T. , Mitsui, T. ,1995a. Intracellular transduction in the regulation of pheromone biosynthesis of the silkworm, Bombyx mori: suggested involvement of calmodulin and phosphoprotein phosphatase. Biosci. Biotechnol. Biochem. 59, 560-562.
    108. Matsumoto, S. , Ozawa, R. , Uchiumi, K. , Kurihara, M. , Mitsui, T. ,1995b. Intracellular signal transduction of PBAN action in the common cutworm, Spodoptera litura: effects of pharmacological agents on sex pheromone production in vitro. Insect Biochem. Mol. Biol. 25, 1055-1059.
    109. Matsumoto, S. , Yamashita, O. , Fonagy, A. , Kurihara, M. , Uchiumi, K. , Nagamine, T. , Mitsui, T. ,1992. Functional diversity of a pheromonotropic neuropeptide - Induction of cuticular melanization and embryonic diapause in Lepidopteran Insects by Pseudaletia pheromonotropin. J. Insect Physiol. 38, 847-851.
    110. Melcher, C. , Bader, R. , Pankratz, M.J. ,2007. Amino acids, taste circuits, and feeding behavior in Drosophila: towards understanding the psychology of feeding in flies and man. J. Endocrinol. 192, 467-472.
    111. Melcher, C. , Pankratz, M.J. ,2005. Candidate gustatory interneurons modulating feeding behavior in the Drosophila brain. PLoS Biol. 3, e305.
    112. Meng, X. , Wahlstrom, G. , Immonen, T. , Kolmer, M. , Tirronen, M. , Predel, R. , Kalkkinen, N. , Heino, T.I. , Sariola, H. , Roos, C. ,2002. The Drosophila hugin gene codes for myostimulatory and ecdysis-modifying neuropeptides. Mech. Dev. 117, 5-13.
    113. Miyamoto, T. , Yamamoto, M. , Ono, A. , Ohtani, K. , Ando, T. ,1999. Substrate specificity of the epoxidation reaction in sex pheromone biosynthesis of the Japanese giant looper (Lepidoptera: Geometridae). Insect Biochem. Mol. Biol. 29, 63-69.
    114. Nachman, R.J. , Ben Aziz, O. , Davidovitch, M. , Zubrzak, P. , Isaac, R.E. , Strey, A. , Reyes-Rangel, G. , Juaristi, E. , Williams, H.J. , Altstein, M. ,2009a. Biostable beta-amino acid PK/PBAN analogs: agonist and antagonist properties. Peptides 30, 608-615.
    115. Nachman, R.J. , Holman, G.M. , Cook, B.J. ,1986. Active fragments and analogs of the insect neuropeptide leucopyrokinin: structurefunction studies. Biochem. Biophys. Res. Commun. 137, 936-942.
    116. Nachman, R.J. , Holman, G.M. , Haddon, W.F. ,1993. Leads for insect neuropeptide mimetic development. Arch. Insect. Biochem. Physiol. 22, 181-197.
    117. Nachman, R.J. , Kim, Y.J. , Wang, X.J. , Etzkorn, F.A. , Kaczmarek, K. , Zabrocki, J. , Adams, M.E. ,2009b. Potent activity of a PK/ PBAN analog with an (E)-alkene, trans-Pro mimic identifies the Pro orientation and core conformation during interaction with HevPBANR-C receptor. Bioorg. Med. Chem. 17, 4216-4220.
    118. Nachman, R.J. , Teal, P.E. , Aziz, O.B. , Davidovitch, M. , Zubrzak, P. , Altstein, M. ,2009c. An amphiphilic, PK/PBAN analog is a selective pheromonotropic antagonist that penetrates the cuticle of a Heliothine insect. Peptides 30, 616-621.
    119. Nachman, R.J. , Teal, P.E. , Radel, P.A. , Holman, G.M. , Abernathy, R.L. ,1996. Potent pheromonotropic/myotropic activity of a carboranyl pseudotetrapeptide analogue of the insect pyrokinin/ PBAN neuropeptide family administered via injection or topical application. Peptides 17, 747-752.
    120. Nachman, R.J. , Teal, P.E. , Ujvary, I. ,2001. Comparative topical pheromonotropic activity of insect pyrokinin/PBAN amphiphilic analogs incorporating different fatty and/or cholic acid components. Peptides 22, 279-285.
    121. Nachman, R.J. , Wang, X.J. , Etzkorn, F.A. , Aziz, O.B. , Davidovitch, M. , Kaczmarek, K. , Zabrocki, J. , Strey, A. , Pryor, N. , Altstein, M. ,2009d. Evaluation of a PK/PBAN analog with an (E)-alkene, trans-Pro isostere identifies the Pro orientation for activity in four diverse PK/PBAN bioassays. Peptides 30, 1254-1259.
    122. Nassel, D.R. ,2002. Neuropeptides in the nervous system of Drosophila and other insects: multiple roles as neuromodulators and neurohormones. Prog. Neurobiol. 68, 1-84.
    123. Nassel, D.R. , Homberg, U. ,2006. Neuropeptides in interneurons of the insect brain. Cell Tissue Res. 326, 1-24.
    124. Nassel, D.R. , Winther, A.M. ,2002. Neuronal co-localization of different isoforms of tachykinin-related peptides (LemTRPs) in the cockroach brain. Cell Tissue Res. 308, 225-239.
    125. Nassel, D.R. , Winther, A.M. ,2010. Drosophila neuropeptides in regulation of physiology and behavior. Prog. Neurobiol. 92, 42-104.
    126. Nassel, D.R. , Zandawala, M. ,2019. Recent advances in neuropeptide signaling in Drosophila, from genes to physiology and behavior. Prog. Neurobiol. 179, 101607.
    127. Ohnishi, A. , Hull, J.J. , Matsumoto, S. ,2006. Targeted disruption of genes in the Bombyx mori sex pheromone biosynthetic pathway. Proc. Natl. Acad. Sci. U. S. A. 103, 4398-4403.
    128. Pietrantonio, P.V. , Xiong, C. , Nachman, R.J. , Shen, Y. ,2018. G protein-coupled receptors in arthropod vectors: omics and pharmacological approaches to elucidate ligand-receptor interactions and novel organismal functions. Curr. Opin. Insect Sci. 29, 12-20.
    129. Plech, A. , Rykaczewska-Czerwinska, M. , Konopinska, D. ,2004. Leucopyrokinin (LPK) analog [d-Ala(5)]-[2-8]-LPK inhibits LPKinduced analgesia in rats. Peptides 25, 1005-1011.
    130. Predel, R. , Neupert, S. , Garczynski, S.F. , Crim, J.W. , Brown, M.R. , Russell, W.K. , Kahnt, J. , Russell, D.H. , Nachman, R.J. ,2010. Neuropeptidomics of the mosquito Aedes aegypti. J. Proteome Res. 9, 2006-2015.
    131. Rafaeli, A. ,2009. Pheromone biosynthesis activating neuropeptide (PBAN): regulatory role and mode of action. Gen. Comp. Endocrinol. 162, 69-78.
    132. Rafaeli, A. , Bober, R. , Becker, L. , Choi, M.Y. , Fuerst, E.J. , Jurenka, R.A. ,2007. Spatial distribution and differential expression of the PBAN receptor in tissues of adult Helicoverpa spp. (Lepidoptera: Noctuidae). Insect Mol. Biol. 16, 287-293.
    133. Rafaeli, A. , Gileadi, C. ,1995. Modulation of the PBAN-stimulated pheromonotropic activity in Helicoverpa armigera. Insect Biochem. Mol. Biol. 25, 827-834.
    134. Rafaeli, A. , Gileadi, C. ,1996. Down regulation of pheromone biosynthesis: cellular mechanisms of pheromonostatic responses. Insect Biochem. Mol. Biol. 26, 797-807.
    135. Rafaeli, A. , Soroker, V. ,1994. Second messenger interactions in response to PBAN stimulation of pheromone gland cultures., in: Borkovec, A., Loeb, M.J. (Eds.), Insect Neurochemistry and Neurophysiology. CRC Press, Boca Raton.
    136. Raina, A.K. ,1993. Neuroendocrine control of sex pheromone biosynthesis in Lepidoptera. Annu. Rev. Entomol. 38, 329-349.
    137. Raina, A.K. , Jaffe, H. , Kempe, T.G. , Keim, P. , Blacher, R.W. , Fales, H.M. , Riley, C.T. , Klun, J.A. , Ridgway, R.L. , Hayes, D.K. ,1989. Identification of a neuropeptide hormone that regulates sex pheromone production in female moths. Science 244, 796-798.
    138. Raina, A.K. , Kempe, T.G. ,1990. A pentapeptide of the C-terminal sequence of PBAN with pheromonotropic activity. Insect Biochem. 20, 849-851.
    139. Raina, A.K. , Klun, J.A. ,1984. Brain factor control of sex pheromone production in the female corn earworm moth. Science 225, 531-533.
    140. Raina, A.K. , Rafaeli, A. , Kingan, T.G. ,1994. Pheromonotropic activity of orally administered PBAN and its analogues in Helicoverpa zea. J. Insect Physiol. 40, 393-397.
    141. Raina, A.K. , Wergin, W.P. , Murphy, C.A. , Erbe, E.F. ,2000. Structural organization of the sex pheromone gland in Helicoverpa zea in relation to pheromone production and release. Arthropod Struct. Dev. 29, 343-353.
    142. Ramaswamy, S.B. , Jurenka, R.A. , Linn, C.E., Jr. , Roelofs, W.L. ,1995. Evidence for the presence of a pheromonotropic factor in hemolymph and regulation of sex pheromone production in Helicoverpa zea. J. Insect Physiol. 41, 501-508.
    143. Ramaswamy, S.B. , Mbata, G.N. , Cohen, N.E. , Moore, A. , Cox, N.M. ,1994. Pheromonotropic and pheromonostatic activity in moths. Arch. Insect. Biochem. Physiol. 25, 301-315.
    144. Sato, Y. , Oguchi, M. , Menjo, N. , Imai, K. , Saito, H. , Ikeda, M. , Isobe, M. , Yamashita, O. ,1993. Precursor polyprotein for multiple neuropeptides secreted from the suboesophageal ganglion of the silkworm Bombyx mori: characterization of the cDNA encoding the diapause hormone precursor and identification of additional peptides. Proc. Natl. Acad. Sci. U. S. A. 90, 3251-3255.
    145. Scherkenbeck, J. , Zdobinsky, T. ,2009. Insect neuropeptides: struc tures, chemical modifications and potential for insect control. Bioorg. Med. Chem. 17, 4071-4084.
    146. Schoofs, L. , De Loof, A. , Van Hiel, M.B. ,2017. Neuropeptides as Regulators of Behavior in Insects. Annu. Rev. Entomol. 62, 35-52.
    147. Schoofs, L. , Vanden Broeck, J. , De Loof, A. ,1993. The myotropic peptides of Locusta migratoria: structures, distribution, functions and receptors. Insect Biochem. Mol. Biol. 23, 859-881.
    148. Senthilkumar, R. , Srinivasan, R. ,2019. Sex-specific spatial and temporal gene expressions of pheromone biosynthesis activating neuropeptide (PBAN) and binding proteins (PBP/OBP) in Spoladea recurvalis. Sci. Rep. 9, 3515.
    149. Shi, Y. , Nachman, R.J. , Gui, S.H. , Piot, N. , Kaczmarek, K. , Zabrocki, J. , Dow, J.A.T. , Davies, S.A. , Smagghe, G. ,2021. Efficacy and biosafety assessment of neuropeptide CAPA analogues against the peach-potato aphid (Myzus persicae). Insect Sci. (in press).
    150. Southey, B.R. , Sweedler, J.V. , Rodriguez-Zas, S.L. ,2008. Prediction of neuropeptide cleavage sites in insects. Bioinformatics 24, 815-825.
    151. Suang, S. , Manaboon, M. , Singtripop, T. , Hiruma, K. , Kaneko, Y. , Tiansawat, P. , Neumann, P. , Chantawannakul, P. ,2017. Larval diapause termination in the bamboo borer, Omphisa fuscidentalis. PLoS ONE 12, e0174919.
    152. Sun, J.S. , Zhang, T.Y. , Zhang, Q.R. , Xu, W.H. ,2003. Effect of the brain and suboesophageal ganglion on pupal development in Helicoverpa armigera through regulation of FXPRLamide neuropeptides. Regul. Pept. 116, 163-171.
    153. Teal, P.E. , Meredith, J.A. , Nachman, R.J. ,1999a. Comparison of rates of penetration through insect cuticle of amphiphylic analogs of insect pyrokinin neuropeptides. Peptides 20, 63-70.
    154. Teal, P.E. , Nachman, R.J. ,1997. Prolonged pheromonotropic activity of pseudopeptide mimics of insect pyrokinin neuropeptides after topical application or injection into a moth. Regul. Pept. 72, 161-167.
    155. Teal, P.E. , Tumlinson, J.H. , Oberlander, H. ,1989. Neural regulation of sex pheromone biosynthesis in Heliothis moths. Proc. Natl. Acad. Sci. U. S. A. 86, 2488-2492.
    156. Teal, P.E.A., Davis, N.T. , Meredith, J.A. , Christensen, T.A. , Hildebrand, J.G. ,1999b. Role of the ventral nerve cord and terminal abdominal ganglion in the regulation of sex pheromone production in the tobacco budworm (Lepidoptera : noctuidae). Ann. Entomol. Soc. Am. 92, 891-901.
    157. Thyagaraja, B.S. , Raina, A.K. ,1994. Regulation of pheromone production in the gypsy moth, Lymantria dispar, and development of an in vivo bioassay. J. Insect Physiol. 40, 969-974.
    158. Tillman, J.A. , Seybold, S.J. , Jurenka, R.A. , Blomquist, G.J. ,1999. Insect pheromones-an overview of biosynthesis and endocrine regulation. Insect Biochem. Mol. Biol. 29, 481-514.
    159. Van Hiel, M.B. , Van Loy, T. , Poels, J. , Vandersmissen, H.P. , Verlinden, H. , Badisco, L. , Broeck, J.V. ,2010. Neuropeptide receptors as possible targets for development of insect pest control agents, in: Geary, T.G., Maule, A.G. (Eds.), Neuropeptide Systems as Targets for Parasite and Pest Control. Springer, New York, pp. 211-226.
    160. Vanden Broeck, J. ,2001. Neuropeptides and their precursors in the fruitfly, Drosophila melanogaster. Peptides 22, 241-254.
    161. Veenstra, J.A. ,2000. Mono- and dibasic proteolytic cleavage sites in insect neuroendocrine peptide precursors. Arch. Insect. Biochem. Physiol. 43, 49-63.
    162. Veenstra, J.A. ,2016. Neuropeptide evolution: Chelicerate neurohormone and neuropeptide genes may reflect one or more whole genome duplications. Gen. Comp. Endocrinol. 229, 41-55.
    163. Watanabe, K. , Hull, J.J. , Niimi, T. , Imai, K. , Matsumoto, S. , Yaginuma, T. , Kataoka, H. ,2007. FXPRL-amide peptides induce ecdysteroidogenesis through a G-protein coupled receptor expressed in the prothoracic gland of Bombyx mori. Mol. Cell. Endocrinol. 273, 51-58.
    164. Wegener, C. , Reinl, T. , Jansch, L. , Predel, R. ,2006. Direct mass spectrometric peptide profiling and fragmentation of larval peptide hormone release sites in Drosophila melanogaster reveals tagmaspecific peptide expression and differential processing. J. Neurochem. 96, 1362-1374.
    165. Wei, W. , Miyamoto, T. , Endo, M. , Murakawa, T. , Pu, G.Q. , Ando, T. ,2003. Polyunsaturated hydrocarbons in the hemolymph: biosynthetic precursors of epoxy pheromones of geometrid and arctiid moths. Insect Biochem. Mol. Biol. 33, 397-405.
    166. Wei, W. , Yamamoto, M. , Asato, T. , Fujii, T. , Pu, G.Q. , Ando, T. ,2004a. Selectivity and neuroendocrine regulation of the precursor uptake by pheromone glands from hemolymph in geometrid female moths, which secrete epoxyalkenyl sex pheromones. Insect Biochem. Mol. Biol. 34, 1215-1224.
    167. Wei, Z.-J. , Hong, G.-Y. , Jinag, S.-T. , Tong, Z.-X. , Lu, C. ,2008. Characters and expression of the gene encoding DH, PBAN and other FXPRLamide family neuropeptides in Antheraea pernyi. J. Appl. Entomol. 132, 59-67.
    168. Wei, Z.-J. , Zhang, T.Y. , Sun, J.S. , Xu, A.Y. , Xu, W.H. , Denlinger, D.L. ,2004b. Molecular cloning, developmental expression, and tissue distribution of the gene encoding DH, PBAN and other FXPRL neuropeptides in Samia cynthia ricini. J. Insect Physiol. 50, 1151-1161.
    169. Xiong, C. , Yang, Y. , Nachman, R.J. , Pietrantonio, P.V. ,2021. Tick CAPA propeptide cDNAs and receptor activity of endogenous tick pyrokinins and analogs: Towards discovering pyrokinin function in ticks. Peptides 146, 170665.
    170. Xu, W. , Sato, Y. , Yamashita, O. ,1999. Molecular characterization of the cDNA encoding diapause hormone and pheromone biosynthesis activating neuropeptide in Bombyx mandarina. J. Seri. Sci. Jpn. 68, 373-379.
    171. Xu, W.H. , Denlinger, D.L. ,2003. Molecular characterization of prothoracicotropic hormone and diapause hormone in Heliothis virescens during diapause, and a new role for diapause hormone. Insect Mol. Biol. 12, 509-516.
    172. Xu, W.H. , Sato, Y. , Ikeda, M. , Yamashita, O. ,1995. Stagedependent and temperature-controlled expression of the gene encoding the precursor protein of diapause hormone and pheromone biosynthesis activating neuropeptide in the silkworm, Bombyx mori. J. Biol. Chem. 270, 3804-3808.
    173. Yeoh, J.G.C. , Pandit, A.A. , Zandawala, M. , Nassel, D.R. , Davies, S.A. , Dow, J.A.T. ,2017. DINeR: Database for insect neuropeptide research. Insect Biochem. Mol. Biol. 86, 9-19.
    174. Zdarek, J. , Nachman, R.J. , Hayes, T.K. ,1997. Insect neuropeptides of the pyrokinin/PBAN family accelerate pupariation in the fleshfly (Sarcophaga bullata) larvae. Ann. N. Y. Acad. Sci. 814, 67- 72.
    175. Zdarek, J. , Nachman, R.J. , Hayes, T.K. ,1998. Structure-activity relationships of insect neuropeptides of the pyrokinin/PBAN family and their selective action on pupariation in flesh fly (Neobelleria bullata) larvae (Diptera, Sarcophagidae). Eur. J. Entomol. 95, 9-16.
    176. Zeltser, I. , Ben-Aziz, O. , Schefler, I. , Bhargava, K. , Altstein, M. , Gilon, C. ,2001. Insect neuropeptide antagonist. Part II. Synthesis and biological activity of backbone cyclic and precyclic PBAN antagonists. J. Pept. Res. 58, 275-284.
    177. Zeltser, I. , Gilon, C. , Ben-Aziz, O. , Schefler, I. , Altstein, M. ,2000. Discovery of a linear lead antagonist to the insect pheromone biosynthesis activating neuropeptide (PBAN). Peptides 21, 1457-1465.
    178. Zhang, Q. , Nachman, R.J. , Zubrzak, P. , Denlinger, D.L. ,2009. Conformational aspects and hyperpotent agonists of diapause hormone for termination of pupal diapause in the corn earworm. Peptides 30, 596-602.
    179. Zhang, Q.R. , Nachman, R.J. , Kaczmarek, K. , Zabrocki, J. , Denlinger, D.L. ,2011. Disruption of insect diapause using agonists and an antagonist of diapause hormone. Proc. Natl. Acad. Sci. U. S. A. 108, 16922-16926.
    180. Zhang, T.Y. , Sun, J.S. , Zhang, L.B. , Shen, J.L. , Xu, W.H. ,2004. Cloning and expression of the cDNA encoding the FXPRL family of peptides and a functional analysis of their effect on breaking pupal diapause in Helicoverpa armigera. J. Insect Physiol. 50, 25-33.
    181. Zhu, J.W. , Millar, J. , Lofstedt, C. ,1995. Hormonal regulation of sex pheromone biosynthesis in the turnip moth, Agrotis segetum. Arch. Insect. Biochem. Physiol. 30, 41-59.
    182. Zubrzak, P. , Williams, H. , Coast, G.M. , Isaac, R.E. , Reyes-Rangel, G. , Juaristi, E. , Zabrocki, J. , Nachman, R.J. ,2007. Beta-amino acid analogs of an insect neuropeptide feature potent bioactivity and resistance to peptidase hydrolysis. Biopolymers 88, 76-82.