Skip to main content

Natural Products from Photorhabdus and Other Entomopathogenic Bacteria

  • Chapter
  • First Online:
The Molecular Biology of Photorhabdus Bacteria

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 402))

Abstract

Although the first natural products (NP) from Photorhabdus and Xenorhabdus bacteria have been known now for almost 30 years, a huge variety of new compounds have been identified in the last 5–10 years, mainly due to the application of modern mass spectrometry. Additionally, application of molecular methods that allow the activation of NP production in several different strains as well as efficient heterologous expression methods have led to the production and validation of many new compounds. In this chapter we discuss the benefit of using Photorhabdus as a model system for microbial chemical ecology. We also examine non-ribosomal peptide synthetases as the most important pathway for NP production. Finally, we discuss the origin and function of all currently known NPs and the development of the molecular and chemical tools used to identify these NPs faster.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ackermann M (2015) A functional perspective on phenotypic heterogeneity in microorganisms. Nat Publishing Group 13:497–508

    CAS  Google Scholar 

  • Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J et al (2012) Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat Prod Rep 30:108–160

    Article  Google Scholar 

  • Bai X, Adams BJ, Ciche TA, Clifton S, Gaugler R, Kim K-S, Spieth J, Sternberg PW, Wilson RK, Grewal PS (2013) A lover and a fighter: the genome sequence of an entomopathogenic nematode heterorhabditis bacteriophora. PLoS One 8:e69618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biggins JB, Liu X, Feng Z, Brady SF (2011) Metabolites from the induced expression of cryptic single operons found in the genome of Burkholderia pseudomallei. J Am Chem Soc 133:1638–1641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biggins JB, Kang H-S, Ternei MA, DeShazer D, Brady SF (2014) The chemical arsenal of Burkholderia pseudomalleiIs essential for pathogenicity. J Am Chem Soc 136:9484–9490

    Article  CAS  PubMed  PubMed Central  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 

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

    Article  CAS  PubMed  Google Scholar 

  • Bode HB, Reimer D, Fuchs SW, Kirchner F, Dauth C, Kegler C, Lorenzen W, Brachmann AO, Grün P (2012) Determination of the absolute configuration of peptide natural products by using stable isotope labeling and mass spectrometry. Chem Eur J 18:2342–2348

    Article  CAS  PubMed  Google Scholar 

  • Bode E, Brachmann AO, Kegler C, Simsek R, Dauth C, Zhou Q, Kaiser M, Klemmt P, Bode HB (2015a) Simple “on-demand” production of bioactive natural products. ChemBioChem 16:1115–1119

    Article  CAS  PubMed  Google Scholar 

  • Bode HB, Brachmann AO, Jadhav KB, Seyfarth L, Dauth C, Fuchs SW, Kaiser M, Waterfield NR, Sack H, Heinemann SH et al (2015b) Structure elucidation and activity of kolossin A, the D-/L-Pentadecapeptide product of a giant nonribosomal peptide synthetase. Angew Chem Int Ed Engl 54:10352–10355

    Article  CAS  PubMed  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 inphotorhabdus luminescens. ChemBioChem 8:1721–1728

    Article  CAS  PubMed  Google Scholar 

  • Brachmann AO, Kirchner F, Kegler C, Kinski SC, Schmitt I, Bode HB (2012) Triggering the production of the cryptic blue pigment indigoidine from Photorhabdus luminescens. J Biotechnol 157:96–99

    Article  CAS  PubMed  Google Scholar 

  • Brachmann AO, Brameyer S, Kresovic D, Hitkova I, Kopp Y, Manske C, Schubert K, Bode HB, Heermann R (2013) Pyrones as bacterial signaling molecules. Nat Chem Biol 9:573–578

    Article  CAS  PubMed  Google Scholar 

  • Brameyer S, Kresovic D, Bode HB, Heermann R (2015) Dialkylresorcinols as bacterial signaling molecules. Proc Natl Acad Sci U.S.A. 112:572–577

    Google Scholar 

  • Brinkman AB, Ettema TJG, De Vos WM, Van Der Oost J (2003) The Lrp family of transcriptional regulators. Mol Microbiol 48:287–294

    Article  CAS  PubMed  Google Scholar 

  • Buscató EL, Büttner D, Brüggerhoff A, Klingler F-M, Weber J, Scholz B, Živković A, Marschalek R, Stark H, Steinhilber D et al (2013) From a multipotent stilbene to soluble epoxide hydrolase inhibitors with antiproliferative properties. ChemMedChem 8:919–923

    Article  PubMed  Google Scholar 

  • Caboche S, Leclere V, Pupin M, Kucherov G, Jacques P (2010) Diversity of monomers in nonribosomal peptides: towards the prediction of origin and biological activity. J Bacteriol 192:5143–5150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cantley AM, Clardy J (2015) Animals in a bacterial world: opportunities for chemical ecology. Nat Prod Rep 32:888–892

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiocchini C, Linne U, Stachelhaus T (2006) In vivo biocombinatorial synthesis of lipopeptides by COM domain-mediated reprogramming of the surfactin biosynthetic complex. Chem Biol 13:899–908

    Article  CAS  PubMed  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  CAS  PubMed  PubMed Central  Google Scholar 

  • Cosmina P, Rodriguez F, de Ferra F, Grandi G, Perego M, Venema G, van Sinderen D (1993) Sequence and analysis of the genetic locus responsible for surfactin synthesis in Bacillus subtilis. Mol Microbiol 8:821–831

    Article  CAS  PubMed  Google Scholar 

  • Coulthurst SJ, Barnard AML, Salmond GPC (2005) Regulation and biosynthesis of carbapenem antibiotics in bacteria. Nat Rev Micro 3:295–306

    Article  CAS  Google Scholar 

  • Cowles KN, Cowles CE, Richards GR, Martens EC, Goodrich-Blair H (2007) The global regulator Lrp contributes to mutualism, pathogenesis and phenotypic variation in the bacterium Xenorhabdus nematophila. Cell Microbiol 9:1311–1323

    Article  CAS  PubMed  Google Scholar 

  • Crawford JM, Portmann C, Zhang X, Roeffaers MBJ, Clardy J (2012) Small molecule perimeter defense in entomopathogenic bacteria. Proc Natl Acad Sci U.S.A. 109:10821–10826

    Google Scholar 

  • Davies J, Ryan KS (2012) Introducing the parvome: bioactive compounds in the microbial world. ACS Chem Biol 7:252–259

    Article  CAS  PubMed  Google Scholar 

  • Davies J, Spiegelman GB, Yim G (2006) The world of subinhibitory antibiotic concentrations. Curr Opin Microbiol 9:445–453

    Article  CAS  PubMed  Google Scholar 

  • De Lay N, Schu DJ, Gottesman S (2013) Bacterial small RNA-based negative regulation: Hfq and its accomplices. J Biol Chem 288:7996–8003

    Article  PubMed  PubMed Central  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  CAS  PubMed  PubMed Central  Google Scholar 

  • Dillman AR, Macchietto M, Porter CF, Rogers A, Williams B, Antoshechkin I, Lee M-M, Goodwin Z, Lu X, Lewis EE et al (2015) Comparative genomics of steinernema reveals deeply conserved gene regulatory networks. Genome Biol 1–21

    Google Scholar 

  • Dorrestein PC, Mazmanian SK, Knight R (2014) Finding the missing links among metabolites, microbes, and the host. Immunity 40:824–832

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dudnik A, Bigler L, Dudler R (2013) Heterologous expression of a Photorhabdus luminescens syrbactin-like gene cluster results in production of the potent proteasome inhibitor glidobactin A. Microbiol Res 168:73–76

    Article  CAS  PubMed  Google Scholar 

  • Erol Ö, Schäberle TF, Schmitz A, Rachid S, Gurgui C, Omari, EM, Lohr F, Kehraus S, Piel J, Müller R et al (2010) Biosynthesis of the myxobacterial antibiotic corallopyronin A. ChemBioChem 11:1253–1265

    Google Scholar 

  • Felnagle EA, Jackson EE, Chan YA, Podevels AM, Berti AD, McMahon MD, Thomas MG (2008) Nonribosomal peptide synthetases involved in the production of medically relevant natural products. Mol Pharm 5:191–211

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu J, Bian X, Hu S, Wang H, Huang F, Seibert PM, Plaza A, Xia L, Müller R, Stewart AF et al (2012a) Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting. Nat Biotechnol 30:440–446

    Google Scholar 

  • Fu J, Bian X, Hu S, Wang H, Huang F, Seibert PM, Plaza A, Xia L, Stewart AF, ller RMU et al (2012b) Full-length RecE enhances linear-linear homologous recombination and facilitates direct cloning for bioprospecting. Nat Biotechnol 30:440–446

    Google Scholar 

  • Fuchs SW, Bozhüyük KAJ, Kresovic D, Grundmann F, Dill V, Brachmann AO, Waterfield NR, Bode HB (2013) Formation of 1,3-cyclohexanediones and resorcinols catalyzed by a widely occurring ketosynthase. Angew Chem Int Ed 52:4108–4112

    Article  CAS  Google Scholar 

  • Gokhale RS, Khosla C (2000) Role of linkers in communication between protein modules. Curr Opin Chem Biol 4:22–27

    Article  CAS  PubMed  Google Scholar 

  • Grünewald J, Marahiel MA (2006) Chemoenzymatic and template-directed synthesis of bioactive macrocyclic peptides. Microbiol Mol Biol Rev 70:121–146

    Article  PubMed  PubMed Central  Google Scholar 

  • Gulick AM (2009) Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase. ACS Chem Biol 4:811–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hahn M, Stachelhaus T (2004) Selective interaction between nonribosomal peptide synthetases is facilitated by short communication-mediating domains. Proc Natl Acad Sci 101:15585–15590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hahn M, Stachelhaus T (2006) Harnessing the potential of communication-mediating domains for the biocombinatorial synthesis of nonribosomal peptides. Proc Natl Acad Sci 103:275–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hang HC, Linder ME (2011) Exploring protein lipidation with chemical biology. Chem Rev 111:6341–6358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hang HC, Geutjes E-J, Grotenbreg G, Pollington AM, Bijlmakers MJ, Ploegh HL (2007) Chemical probes for the rapid detection of fatty-acylated proteins in mammalian cells. J Am Chem Soc 129:2744–2745

    Article  CAS  PubMed  Google Scholar 

  • Hernandez-Lucas I, Calva E (2012) The coming of age of the LeuO regulator. Mol Microbiol 85:1026–1028

    Article  CAS  PubMed  Google Scholar 

  • Hu K, Li J, Li B, Webster JM, Chen G (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  CAS  PubMed  Google Scholar 

  • Ikeda H, Ishikawa J, Hanamoto A, Shinose M, Kikuchi H, Shiba T, Sakaki Y, Hattori M, Ōmura S (2003) Complete genome sequence and comparative analysis of the industrial microorganism streptomyces avermitilis. Nat Biotechnol 21:526–531

    Article  PubMed  Google Scholar 

  • Jewett JC, Bertozzi CR (2010) Cu-free click cycloaddition reactions in chemical biology. Chem Soc Rev 39:1272–1279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ji D, Yi Y, Kang G-H, Choi Y-H, Kim P, Baek N-I, Kim Y (2004) Identification of an antibacterial compound, benzylideneacetone, from Xenorhabdus nematophilaagainst major plant-pathogenic bacteria. FEMS Microbiol Lett 239:241–248

    Article  CAS  PubMed  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 

  • Kolb HC, Finn MG, Sharpless KB (2001) Click-Chemie: diverse chemische Funktionalität mit einer Handvoll guter Reaktionen. Angew Chem 113:2056–2075

    Article  Google Scholar 

  • Kontnik R, Crawford JM, Clardy J (2010) Exploiting a global regulator for small molecule discovery in Photorhabdus luminescens. ACS Chem Biol 5:659–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kresovic D, Schempp F, Cheikh-Ali Z, Bode HB (2015) A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis. Beilstein J Org Chem 11:1412–1417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lautru S, Challis GL (2004) Microbiology 150(Pt 6):1629–1636. Review. PMID: 15184549

    Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schäberle TF, Hughes DE, Epstein S et al (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517:455–459

    Google Scholar 

  • Marahiel MA (2016) A structural model for multimodular NRPS assembly lines. Nat Prod Rep 33:136–140

    Article  CAS  PubMed  Google Scholar 

  • Mootz HD, Marahiel MA (1997) The tyrocidine biosynthesis operon of Bacillus brevis: complete nucleotide sequence and biochemical characterization of functional internal adenylation domains. J Bacteriol 179:6843–6850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mootz HD, Schwarzer D, Marahiel MA (2002) Ways of assembling complex natural products on modular nonribosomal peptide synthetases. ChemBioChem 3:490–504

    Article  CAS  PubMed  Google Scholar 

  • Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nollmann FI, Dauth C, Mulley G, Kegler C, Kaiser M, Waterfield NR, Bode HB (2015a) Insect-specific production of new GameXPeptides in Photorhabdus luminescens TTO1, widespread natural products in entomopathogenic bacteria. ChemBioChem 16:205–208

    Article  CAS  PubMed  Google Scholar 

  • Nollmann FI, Heinrich AK, Brachmann AO, Morisseau C, Mukherjee K, Casanova-Torres ÁM, Strobl F, Kleinhans D, Kinski S, Schultz K et al (2015b) A Photorhabdus natural product inhibits insect juvenile hormone epoxide hydrolase. ChemBioChem 16:766–771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Omura S, Ikeda H, Ishikawa J, Hanamoto A, Takahashi C, Shinose M, Takahashi Y, Horikawa H, Nakazawa H, Osonoe T et al (2001) Genome sequence of an industrial microorganism streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci 98:12215–12220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pérez AJ, Wesche F, Adihou H, Bode HB (2016) Solid-phase enrichment and analysis of azide-labeled natural products: fishing downstream of biochemical pathways. Chemistry 22:639–645

    Article  PubMed  Google Scholar 

  • Scharf DH, Brakhage AA (2013) Engineering fungal secondary metabolism: a roadmap to novel compounds. J Biotechnol 163:179–183

    Article  CAS  PubMed  Google Scholar 

  • Schimming O, Fleischhacker F, Nollmann FI, Bode HB (2014) Yeast homologous recombination cloning leading to the novel peptides ambactin and xenolindicin. ChemBioChem 15:1290–1294

    Article  CAS  PubMed  Google Scholar 

  • Schmitt EK, Hoepfner D, Krastel P (2015) Natural products as probes in pharmaceutical research. J Ind Microbiol Biotechnol 43:249–260

    Article  PubMed  Google Scholar 

  • Schöner TA, Kresovic D, Bode HB (2015) Biosynthesis and function of bacterial dialkylresorcinol compounds. Appl Microbiol Biotechnol 1–6

    Google Scholar 

  • Seo S, Lee S, Hong Y, Kim Y (2012) Phospholipase A2 inhibitors synthesized by two entomopathogenic bacteria, xenorhabdus nematophila and Photorhabdus temperata subsp. temperata. Appl Environ Microbiol 78:3816–3823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharon G, Garg N, Debelius J, Knight R, Dorrestein PC, Mazmanian SK (2014) Specialized metabolites from the microbiome in health and disease. Cell Metab 20:719–730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Stein ML, Beck P, Kaiser M, Dudler R (2012) One-shot NMR analysis of microbial secretions identifies highly potent proteasome inhibitor

    Google Scholar 

  • Sucipto H, Wenzel SC, Müller R (2013) Exploring chemical diversity of α-Pyrone antibiotics: molecular basis of myxopyronin biosynthesis. ChemBioChem 14:1581–1589

    Article  CAS  PubMed  Google Scholar 

  • Theodore CM, King JB, You J, Cichewicz RH (2012) Production of cytotoxic glidobactins/luminmycins by Photorhabdus asymbioticain liquid media and live crickets. J Nat Prod 75:2007–2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tobias NJ, Heinrich AK, Eresmann H, Wright PR, Neubacher N, Backofen R, Bode HB (2016a) Environ Microbiol. Aug 23. doi:10.1111/1462-2920.13502

    Google Scholar 

  • Tobias NJ, Mishra B, Gupta DK, Sharma R, Thines M, Stinear TP, Bode HB (2016b) Genome comparisons provide insights into the role of secondary metabolites in the pathogenic phase of the Photorhabdus life cycle. BMC Genomics

    Google Scholar 

  • Ullah I, Khan A, Ali L, Khan A, Waqas M, Lee I-J, Shin J-H (2014) An Insecticidal compound produced by an insect-pathogenic bacterium suppresses host defenses through phenoloxidase inhibition. Molecules 19:20913–20928

    Article  PubMed  Google Scholar 

  • Ullah I, Khan AL, Ali L, Khan AR, Waqas M, Hussain J, Lee I-J, Shin J-H (2015) Benzaldehyde as an insecticidal, antimicrobial, and antioxidant compound produced by Photorhabdus temperata M1021. J Microbiol 53:127–133

    Article  CAS  PubMed  Google Scholar 

  • Vogel J, Luisi BF (2011) Hfq and its constellation of RNA. Nat Rev Micro 9:578–589

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Helge B. Bode .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Bozhüyük, K.A.J., Zhou, Q., Engel, Y., Heinrich, A., Pérez, A., Bode, H.B. (2016). Natural Products from Photorhabdus and Other Entomopathogenic Bacteria. In: ffrench-Constant, R. (eds) The Molecular Biology of Photorhabdus Bacteria . Current Topics in Microbiology and Immunology, vol 402. Springer, Cham. https://doi.org/10.1007/82_2016_24

Download citation

Publish with us

Policies and ethics