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Insect Biotechnology pp 77–93Cite as

Insect-Associated Microorganisms as a Source for Novel Secondary Metabolites with Therapeutic Potential

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Part of the book series: Biologically-Inspired Systems ((BISY,volume 2))

Abstract

Natural products play an essential role in our everyday life as almost all antibiotics or anti-cancer compounds currently in clinical use are either natural products or derivatives thereof. Mainly due to increasing resistance against these antibiotics there is an urgent need for novel bioactive natural products and several strategies are currently in use to find new compounds. In this chapter insects are suggested as a new and very promising source for novel secondary metabolite-producing bacteria and fungi. Whereas entomopathogenic fungi have been known for quite some time as potent producers of different bioactive compounds and have been used in traditional Chinese medicine for more than 2000 years, almost nothing is known about the underlying biochemistry and molecular biology that is involved in the biosynthesis of such compounds. Similarly, entomopathogenic bacteria have only been proven to be a rich source of interesting compounds during the last 20 years and recent genome sequencing projects have revealed their great potential as secondary metabolite producers. Furthermore, bacteria that live in symbiosis with insects have also been shown to be a rich source of potent natural products which have to be explored in the future in more detail.

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References

  • Azumi M, Ishidoh K, Kinoshita H, Nihira T, Ihara F, Fujita T, Igarashi Y (2008) Aurovertins F-H from the entomopathogenic fungus Metarhizium anisopliae. J Nat Prod 71:278–280

    Article  PubMed  CAS  Google Scholar 

  • Basset A, Khush RS, Braun A, Gardan L, Boccard F, Hoffmann JA, Lemaitre B (2000) The phytopathogenic bacteria Erwinia carotovora infects Drosophila and activates an immune response. Proc Natl Acad Sci USA 97:3376–3381

    Article  PubMed  CAS  Google Scholar 

  • Bode HB, Bethe B, Hofs R, Zeeck A (2002) Big effects from small changes: possible ways to explore nature’s chemical diversity. Chembiochem 3:619–627

    Article  PubMed  CAS  Google Scholar 

  • Bode HB, Müller R (2005) The impact of bacterial genomics on natural product research. Angew Chem Int Ed 44:6828–6846

    Article  CAS  Google Scholar 

  • Brachmann AO, Joyce SA, Jenke-Kodama H, Schwär G, Clarke DJ, Bode HB (2007) A type II polyketide synthase is responsible for anthraquinone biosynthesis in Photorhabdus luminescens. Chembiochem 8:1721–1728

    Article  PubMed  CAS  Google Scholar 

  • Challacombe JF, Altherr MR, Xie G, Bhotika SS, Brown N, Bruce D (2007) The complete genome sequence of Bacillus thuringiensis Al Hakam. J Bacteriol 189:3680–3681

    Article  PubMed  CAS  Google Scholar 

  • Champion OL, Cooper IA, James SL, Ford D, Karlyshev A, Wren BW, Duffield M, Oyston PC, Titball RW (2009) Galleria mellonella as an alternative infection model for Yersinia pseudotuberculosis. Microbiology 155:1516–1522

    Article  PubMed  CAS  Google Scholar 

  • Chapman ADA (2007) Report for the Department of the Environment and Heritage, September 2005. Australian Biodiversity Information Services, Toowoomba, Australia. www.environment.gov.au/biodiversity/abrs/publications/other/species-numbers/03-02-groups-invertebrates.html

  • Chen XH, Koumoutsi A, Scholz R, Borriss R (2009) More than anticipated - production of antibiotics and other secondary metabolites by Bacillus amyloliquefaciens FZB42. J Mol Microbiol Biotechnol 16:14–24

    Article  PubMed  CAS  Google Scholar 

  • Ciche TA, Blackburn M, Carney JR, Ensign JC (2003) Photobactin: a catechol siderophore produced by Photorhabdus luminescens, an entomopathogen mutually associated with Heterorhabditis bacteriophora NC1 nematodes. Appl Environ Microbiol 69:4706–4713

    Article  PubMed  CAS  Google Scholar 

  • Currie CR (2001) A community of ants, fungi, and bacteria: a multilateral approach to studying symbiosis. Annu Rev Microbiol 55:357–380

    Article  PubMed  CAS  Google Scholar 

  • Currie CR, Scott JA, Summerbell RC, Malloch D (1999) Fungus-growing ants use antibiotic-producing bacteria to control garden parasites. Nature 398:701–704

    Article  CAS  Google Scholar 

  • Derzelle S, Duchaud E, Kunst F, Danchin A, Bertin P (2002) Identification, characterization, and regulation of a cluster of genes involved in carbapenem biosynthesis in Photorhabdus luminescens. Appl Environ Microbiol 68:3780–3789

    Article  PubMed  CAS  Google Scholar 

  • Duchaud E, Rusniok C, Frangeul L, Buchrieser C, Givaudan A, Taourit S (2003) The genome sequence of the entomopathogenic bacterium Photorhabdus luminescens. Nat Biotechnol 21:1307–1313

    Article  PubMed  CAS  Google Scholar 

  • Eleftherianos I, Boundy S, Joyce SA, Aslam S, Marshall JW, Cox RJ, Simpson TJ, Clarke DJ, ffrench-Constant RH, Reynolds SE (2007) An antibiotic produced by an insect-pathogenic bacterium suppresses host defenses through phenoloxidase inhibition. Proc Natl Acad Sci USA 104:2419–2424

    Article  PubMed  CAS  Google Scholar 

  • ffrench-Constant R, Waterfield N (2006) An ABC guide to the bacterial toxin complexes. Adv Appl Microbiol 58:169–183

    Article  PubMed  CAS  Google Scholar 

  • Fodor A, Forst S, Haynes L, Hevesi M, Hogan J, Klein MG, Mathe-Fodor A, Stackebrndt E, Szentirmai A, Sztaricskai F, Ersek T, Zeller M (2008) New perspectives of Xenorhabdus antibiotics research. In: Ehlers, RU, Enkerli, J, Glazer, I, Lopez-Ferber, M, and Tkaczuk, C (eds) IOBC/WPRS Bulletin: Insect pathogens and insect parasitic nematodes. IOBC/WPRS, Alès, pp 157–164

    Google Scholar 

  • Goodrich-Blair H, Clarke DJ (2007) Mutualism and pathogenesis in Xenorhabdus and Photorhabdus: two roads to the same destination. Mol Microbiol 64:260–268

    Article  PubMed  CAS  Google Scholar 

  • Gouge DH, Snyder JL (2006) Temporal association of entomopathogenic nematodes (Rhabditida: Steinernematidae and Heterorhabditidae) and bacteria. J Invertebr Pathol 91:147–157

    Article  PubMed  Google Scholar 

  • Grimont PAD, Jackson TA, Ageron E, Noonan MJ (1988) Serratia entomophila sp. nov. associated with amber disease in the New Zealand grass grub Costelytra Zealandica. Int J Syst Bacteriol 38:1–6

    Article  CAS  Google Scholar 

  • Haeder S, Wirth R, Herz H, Spiteller D (2009) Candicidin-producing Streptomyces support leaf-cutting ants to protect their fungus garden against the pathogenic fungus Escovopsis. Proc Natl Acad Sci USA 106:4742–4746

    Article  PubMed  Google Scholar 

  • Han CS, Xie G, Challacombe JF, Altherr MR, Bhotika SS, Bruce D (2006) Pathogenomic sequence analysis of Bacillus cereus and Bacillus thuringiensis isolates closely related to Bacillus anthracis. J Bacteriol 188:3382–3390

    Article  PubMed  Google Scholar 

  • Hawksworth DL, Rossman AY (1997) Where are all the undescribed fungi? Phytopathology 87:888–891

    Article  PubMed  CAS  Google Scholar 

  • Herbert EE, Goodrich-Blair H (2007) Friend and foe: the two faces of Xenorhabdus nematophila. Nat Rev Microbiol 5:634–646

    Article  PubMed  CAS  Google Scholar 

  • Hofstetter RW, Cronin JT, Klepzig KD, Moser JC, Ayres MP (2006) Antagonisms, mutualisms and commensalisms affect outbreak dynamics of the southern pine beetle. Oecologia 147:679–691

    Article  PubMed  Google Scholar 

  • Hu KJ, Li JX, Li B, Webster JM, Chen GH (2006) A novel antimicrobial epoxide isolated from larval Galleria mellonella infected by the nematode symbiont, Photorhabdus luminescens (Enterobacteriaceae). Bioorg Med Chem 14:4677–4681

    Article  PubMed  CAS  Google Scholar 

  • Hywel-Jones NL (2002) The importance of invertebrate-pathogenic fungi from the tropics. Trop Mycol 2:133–144

    Article  Google Scholar 

  • Isaka M, Kittakoop P, Kirtikara K, Hywel-Jones NL, Thebtaranonth Y (2005) Bioactive substances from insect pathogenic fungi. Acc Chem Res 38:813–823

    Article  PubMed  CAS  Google Scholar 

  • Ji D, Yi Y, Kang GH, Choi YH, Kim P, Baek NI, Kim Y (2004) Identification of an antibacterial compound, benzylideneacetone, from Xenorhabdus nematophila against major plant-pathogenic bacteria. FEMS Microbiol Lett 239:241–248

    Article  PubMed  CAS  Google Scholar 

  • Joyce SA, Brachmann AO, Glazer I, Lango L, Schwär G, Clarke DJ, Bode HB (2008) Bacterial biosynthesis of a multipotent stilbene. Angew Chem Int Ed 47:1942–1945

    Article  CAS  Google Scholar 

  • Kaltenpoth M, Goettler W, Dale C, Stubblefield JW, Herzner G, Roeser-Mueller K, Strohm E (2006) ‘Candidatus Streptomyces philanthi’, an endosymbiotic streptomycete in the antennae of Philanthus digger wasps. Int J Syst Evol Microbiol 56:1403–1411

    Article  PubMed  CAS  Google Scholar 

  • Kaltenpoth M, Gottler W, Herzner G, Strohm E (2005) Symbiotic bacteria protect wasp larvae from fungal infestation. Curr Biol 15:475–479

    Article  PubMed  CAS  Google Scholar 

  • Kevany BM, Rasko DA, Thomas MG (2009) Characterization of the complete zwittermicin A biosynthesis gene cluster from Bacillus cereus. Appl Environ Microbiol 75: 1144–1155

    Article  PubMed  CAS  Google Scholar 

  • Kikuchi H, Hoshi T, Kitayama M, Sekiya M, Katou Y, Ueda K, Kubohara Y, Sato H, Shimazu M, Kurata S, Oshima Y (2009) New diterpene pyrone-type compounds, metarhizins A and B, isolated from entomopathogenic fungus, Metarhizium flavoviride and their inhibitory effects on cellular proliferation. Tetrahedron 65:469–477

    Article  CAS  Google Scholar 

  • Krasnoff SB, Keresztes I, Gillilan RE, Szebenyi DM, Donzelli BG, Churchill AC, Gibson DM (2007) Serinocyclins A and B, cyclic heptapeptides from Metarhizium anisopliae. J Nat Prod 70:1919–1924

    Article  PubMed  CAS  Google Scholar 

  • Kroiss J, Kaltenpoth M, Schneider B, Schwinger MG, Hertweck C, Maddula RK, Strohm E, Svatos A (2010) Symbiotic Streptomycetes provide antibiotic combination prophylaxis for wasp offspring. Nat Chem Biol 6: 261–263

    Google Scholar 

  • Lang G, Kalvelage T, Peters A, Wiese J, Imhoff JF (2008) Linear and cyclic peptides from the entomopathogenic bacterium Xenorhabdus nematophilus. J Nat Prod 71:1074–1077

    Article  PubMed  CAS  Google Scholar 

  • Lee SY, Kinoshita H, Ihara F, Igarashi Y, Nihira T (2008) Identification of novel derivative of helvolic acid from Metarhizium anisopliae grown in medium with insect component. J Biosci Bioeng 105:476–480

    Article  PubMed  CAS  Google Scholar 

  • Li J, Chen G, Webster JM, Czyzewska E (1995a) Antimicrobial metabolites from a bacterial symbiont. J Nat Prod 58:1081–1086

    Article  PubMed  CAS  Google Scholar 

  • Li JX, Chen GH, Wu HM, Webster JM (1995b) Identification of two pigments and a hydroxystilbene antibiotic from Photorhabdus luminescens. Appl Environ Microbiol 61:4329–4333

    PubMed  CAS  Google Scholar 

  • Li J, Hu K, Webster JM (1998) Antibiotics from Xenorhabdus spp. and Photorhabdus spp. (Enterobacteriaceae). Chem Hereocycl Compd 34:1331–1339

    Article  CAS  Google Scholar 

  • Matsui T, Tokuda G, Shinzato N (2009) Termites as functional gene resources. Recent Pat Biotechnol 3:10–18

    Article  PubMed  CAS  Google Scholar 

  • McInerney BV, Gregson RP, Lacey MJ, Akhurst RJ, Lyons GR, Rhodes SH, Smith DR, Engelhardt LM, White AH (1991a) Biologically active metabolites from Xenorhabdus spp., Part 1. Dithiolopyrrolone derivatives with antibiotic activity. J Nat Prod 54:774–784

    Article  PubMed  CAS  Google Scholar 

  • McInerney BV, Taylor WC, Lacey MJ, Akhurst RJ, Gregson RP (1991b) Biologically active metabolites from Xenorhabdus spp., Part 2. Benzopyran-1-one derivatives with gastroprotective activity. J Nat Prod 54:785–795

    Article  PubMed  CAS  Google Scholar 

  • Mihara K, Tanabe T, Yamakawa Y, Funahashi T, Nakao H, Narimatsu S, Yamamoto S (2004) Identification and transcriptional organization of a gene cluster involved in biosynthesis and transport of acinetobactin, a siderophore produced by Acinetobacter baumannii ATCC 19606(T). Microbiology 150:2587–2597

    Article  PubMed  CAS  Google Scholar 

  • Mylonakis E (2008) Galleria mellonella and the study of fungal pathogenesis: making the case for another genetically tractable model host. Mycopathologia 165:1–3

    Article  PubMed  Google Scholar 

  • Mylonakis E, Casadevall A, Ausubel FM (2007) Exploiting amoeboid and non-vertebrate animal model systems to study the virulence of human pathogenic fungi. PLoS Pathog 3:e101

    Article  PubMed  CAS  Google Scholar 

  • Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477

    Article  PubMed  CAS  Google Scholar 

  • Oh DC, Poulsen M, Currie CR, Clardy J (2009a) Dentigerumycin: a bacterial mediator of an ant-fungus symbiosis. Nat Chem Biol 5(6):391–393

    Article  PubMed  CAS  Google Scholar 

  • Oh DC, Scott JJ, Currie CR, Clardy J (2009b) Mycangimycin, a polyene peroxide from a mutualist Streptomyces sp. Org Lett 11:633–636

    Article  PubMed  CAS  Google Scholar 

  • Pankewitz F, Hilker M (2008) Polyketides in insects: ecological role of these widespread chemicals and evolutionary aspects of their biogenesis. Biol Rev 83:209–226

    Article  PubMed  Google Scholar 

  • Paterson RRM (2008) Cordyceps: a traditional Chinese medicine and another fungal therapeutic biofactory? Phytochemistry 69:1469–1495

    Article  PubMed  CAS  Google Scholar 

  • Piel J (2002) A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles. Proc Natl Acad Sci USA 99:14002–14007

    Article  PubMed  CAS  Google Scholar 

  • Piel J (2004) Metabolites from symbiotic bacteria. Nat Prod Rep 21:519–538

    Article  PubMed  CAS  Google Scholar 

  • Piel J (2009) Metabolites from symbiotic bacteria. Nat Prod Rep 26:338–362

    Article  PubMed  CAS  Google Scholar 

  • Reimer D, Luxenburger E, Brachmann AO, Bode HB (2009) A new type of pyrrolidine biosynthesis is involved in the late steps of xenocoumacin production in Xenorhabdus nematophila. Chembiochem 10(12):1997–2001

    Article  PubMed  CAS  Google Scholar 

  • Reverchon S, Rouanet C, Expert D, Nasser W (2002) Characterization of indigoidine biosynthetic genes in Erwinia chrysanthemi and role of this blue pigment in pathogenicity. J Bacteriol 184:654–665

    Article  PubMed  CAS  Google Scholar 

  • Samson RA, Evans HC, Latge J-P (1988) Atlas of entomopathogenic fungi. Springer, Heidelberg

    Google Scholar 

  • Santos AV, Dillon RJ, Dillon VM, Reynolds SE, Samuels RI (2004) Ocurrence of the antibiotic producing bacterium Burkholderia sp. in colonies of the leaf-cutting ant Atta sexdens rubropilosa. FEMS Microbiol Lett 239:319–323

    Article  PubMed  CAS  Google Scholar 

  • Scott JJ, Oh DC, Yuceer MC, Klepzig KD, Clardy J, Currie CR (2008) Bacterial protection of beetle-fungus mutualism. Science 322:63

    Article  PubMed  CAS  Google Scholar 

  • Sieber SA, Marahiel MA (2005) Molecular mechanisms underlying nonribosomal peptide synthesis: approaches to new antibiotics. Chem Rev 105:715–738

    Article  PubMed  CAS  Google Scholar 

  • Singh J, Banerjee N (2008) Transcriptional analysis and functional characterization of a gene pair encoding iron-regulated xenocin and immunity proteins of Xenorhabdus nematophila. J Bacteriol 190:3877–3885

    Article  PubMed  CAS  Google Scholar 

  • Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416

    Article  PubMed  CAS  Google Scholar 

  • Takahashi H, Kumagai T, Kitani K, Mori M, Matoba Y, Sugiyama M (2007) Cloning and characterization of a Streptomyces single module type non-ribosomal peptide synthetase catalyzing a blue pigment synthesis. J Biol Chem 282:9073–9081

    Article  PubMed  CAS  Google Scholar 

  • Thaler JO, Baghdiguian S, Boemare N (1995) Purification and characterization of Xenorhabdicin, a phage tail-like bacteriocin, from the lysogenic strain F1 of Xenorhabdus nematophilus. Appl Environ Microbiol 61:2049–2052

    PubMed  CAS  Google Scholar 

  • Thongtan J, Saenboonrueng J, Rachtawee P, Isaka M (2006) An antimalarial tetrapeptide from the entomopathogenic fungus Hirsutella sp BCC 1528. J Nat Prod 69:713–714

    Article  PubMed  CAS  Google Scholar 

  • Vallet-Gely I, Lemaitre B, Boccard F (2008) Bacterial strategies to overcome insect defences. Nat Rev Microbiol 6:302–313

    Article  PubMed  CAS  Google Scholar 

  • Van Lanen SG, Shen B (2008) Advances in polyketide synthase structure and function. Curr Opin Drug Discov Devel 11:186–195

    PubMed  Google Scholar 

  • Vilcinskas A (2009) Lepidopterans as model mini-hosts for human pathogens and as a resource for peptide antibiotics. In: MR Goldsmith, F Marec (eds) Molecular Biology and Genetics of the Lepidoptera, CRC Press, Boca raton, FL, pp 293–305

    Google Scholar 

  • Vodovar N, Vallenet D, Cruveiller S, Rouy Z, Barbe V, Acosta C, Cattolico L, Jubin C, Lajus A, Segurens B, Vacherie B, Wincker P, Weissenbach J, Lemaitre B, Medigue C, Boccard F (2006) Complete genome sequence of the entomopathogenic and metabolically versatile soil bacterium Pseudomonas entomophila. Nat Biotechnol 24:673–679

    Article  PubMed  CAS  Google Scholar 

  • von Nussbaum F, Brands M, Hinzen B, Weigand S, Habich D (2006) Antibacterial natural products in medicinal chemistry-exodus or revival? Angew Chem Int Ed 45:5072–5129

    Article  CAS  Google Scholar 

  • Waterfield NR, Sanchez-Contreras M, Eleftherianos I, Dowling A, Wilkinson P, Parkhill J, Thomson N, Reynolds SE, Bode HB, Dorus S, ffrench-Constant RH (2008) Rapid Virulence Annotation (RVA): identification of virulence factors using a bacterial genome library and multiple invertebrate hosts. Proc Natl Acad Sci USA 105:15967–15972

    Article  PubMed  Google Scholar 

  • Weissman KJ (2007) Mutasynthesis - uniting chemistry and genetics for drug discovery. Trends Biotechnol 25:139–142

    Article  PubMed  CAS  Google Scholar 

  • Weist S, Süssmuth RD (2005) Mutational biosynthesis-a tool for the generation of structural diversity in the biosynthesis of antibiotics. Appl Microbiol Biotechnol 68:141–150

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Orozco R, Kithsiri Wijeratne EM, Espinosa-Artiles P, Leslie Gunatilaka AA, Patricia SS, Molnar I (2009a) Biosynthesis of the cyclooligomer depsipeptide bassianolide, an insecticidal virulence factor of Beauveria bassiana. Fungal Genet Biol 46:353–364

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Orozco R, Wijeratne EM, Gunatilaka AA, Stock SP, Molnar I (2008) Biosynthesis of the cyclooligomer depsipeptide beauvericin, a virulence factor of the entomopathogenic fungus Beauveria bassiana. Chem Biol 15:898–907

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Wijeratne EM, Espinosa-Artiles P, Gunatilaka AA, Molnar I (2009b) Combinatorial mutasynthesis of scrambled beauvericins, cyclooligomer depsipeptide cell migration inhibitors from Beauveria bassiana. Chembiochem 10:345–354

    Article  PubMed  CAS  Google Scholar 

  • Xu Y, Zhan J, Wijeratne EM, Burns AM, Gunatilaka AA, Molnar I (2007) Cytotoxic and Antihaptotactic beauvericin analogues from precursor-directed biosynthesis with the insect pathogen Beauveria bassiana ATCC 7159. J Nat Prod 70:1467–1471

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Choi YL, Sun M, Yu ZN (2008) Novel roles of Bacillus thuringiensis to control plant diseases. Appl Microbiol Biotechnol 80:563–572

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Work in the author’s lab is supported by the Deutsche Forschungsgemein- schaft and the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement No. 223328.

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  1. Molecular Biotechnology, Institute for Molecular Bio Science, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany

    Helge B. Bode

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  1. , Institute of Phytopathology and Applied, University of Giessen, Heinrich-Buff-Ring 26-32, Giessen, 35392, Germany

    Andreas Vilcinskas

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Bode, H.B. (2011). Insect-Associated Microorganisms as a Source for Novel Secondary Metabolites with Therapeutic Potential. In: Vilcinskas, A. (eds) Insect Biotechnology. Biologically-Inspired Systems, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9641-8_5

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