1887

Abstract

Sesquiterpene cyclases (STC) catalyse the cyclization of the C15 molecule farnesyl diphosphate into a vast variety of mono- or polycyclic hydrocarbons and, for a few enzymes, oxygenated structures, with diverse stereogenic centres. The huge diversity in sesquiterpene skeleton structures in nature is primarily the result of the type of cyclization driven by the STC. Despite the phenomenal impact of fungal sesquiterpenes on the ecology of fungi and their potentials for applications, the fungal sesquiterpenome is largely untapped. The identification of fungal STC is generally based on protein sequence similarity with characterized enzymes. This approach has improved our knowledge on STC in a few fungal species, but it has limited success for the discovery of distant sequences. Besides, the tools based on secondary metabolite biosynthesis gene clusters have shown poor performance for terpene cyclases. Here, we used four sets of sequences of fungal STC that catalyse four types of cyclization, and specific amino acid motives to identify phylogenetically related sequences in the genomes of basidiomycetes fungi from the order Polyporales. We validated that four STC genes newly identified from the genome sequence of , each classified in a different phylogenetic clade, catalysed a predicted cyclization of farnesyl diphosphate. We built HMM models and searched STC genes in 656 fungal genomes genomes. We identified 5605 STC genes, which were classified in one of the four clades and had a predicted cyclization mechanism. We noticed that the HMM models were more accurate for the prediction of the type of cyclization catalysed by basidiomycete STC than for ascomycete STC.

Funding
This study was supported by the:
  • Joint Genome Institute (Award DE-SC0019427)
    • Principle Award Recipient: IgorGrigoriev
  • Fondation Aix-Marseille Universite
    • Principle Award Recipient: MargotLoussouarn-Yvon
  • Aix-Marseille Université
    • Principle Award Recipient: JulieCouillaud
  • Groupement de Recherche Génomique Environnementale
    • Principle Award Recipient: HayatHage
  • Conseil Régional Provence-Alpes-Côte d'Azur
    • Principle Award Recipient: HayatHage
  • INRAE
    • Principle Award Recipient: HayatHage
  • Institut Carnot 3BCAR
    • Principle Award Recipient: HayatHage
  • Joint Genome Institute (Award DE-AC02-05CH11231)
    • Principle Award Recipient: IgorGrigoriev
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000990
2023-04-19
2024-05-04
Loading full text...

Full text loading...

/deliver/fulltext/mgen/9/4/mgen000990.html?itemId=/content/journal/mgen/10.1099/mgen.0.000990&mimeType=html&fmt=ahah

References

  1. Christianson DW. Structural and chemical biology of terpenoid cyclases. Chem Rev 2017; 117:11570–11648 [View Article] [PubMed]
    [Google Scholar]
  2. Leeper FJ, Vederas JC. Biosynthesis. In Cyclization Enzymes in the Biosynthesis of Monoterpenes, Sesquiterpenes, and Diterpenes Berlin, Heidelberg: Springer; 2000 pp 53–95 [View Article]
    [Google Scholar]
  3. Christianson DW. Structural biology and chemistry of the terpenoid cyclases. Chem Rev 2006; 106:3412–3442 [View Article] [PubMed]
    [Google Scholar]
  4. Schrader J, Bohlmann J. Biotechnology of isoprenoids. In Biosynthesis of Terpenoid Natural Products in Fungi Cham: Springer International Publishing; 2015 pp 19–61 [View Article]
    [Google Scholar]
  5. Hohn TM, Vanmiddlesworth F. Purification and characterization of the sesquiterpene cyclase trichodiene synthetase from Fusarium sporotrichioides. Arch Biochem Biophys 1986; 251:756–761 [View Article] [PubMed]
    [Google Scholar]
  6. Proctor RH, McCormick SP, Kim H-S, Cardoza RE, Stanley AM et al. Evolution of structural diversity of trichothecenes, a family of toxins produced by plant pathogenic and entomopathogenic fungi. PLoS Pathog 2018; 14:e1006946 [View Article] [PubMed]
    [Google Scholar]
  7. Cane DE, Swanson S, Murthy PPN. Trichodiene biosynthesis and the enzymic cyclization of farnesyl pyrophosphate. J Am Chem Soc 1981; 103:2136–2138 [View Article]
    [Google Scholar]
  8. Tijerino A, Cardoza RE, Moraga J, Malmierca MG, Vicente F et al. Overexpression of the trichodiene synthase gene tri5 increases trichodermin production and antimicrobial activity in Trichoderma brevicompactum. Fungal Genet Biol 2011; 48:285–296 [View Article] [PubMed]
    [Google Scholar]
  9. Kumari I, Chaudhary N, Sandhu P, Ahmed M, Akhter Y. Structural and mechanistic analysis of engineered trichodiene synthase enzymes from Trichoderma harzianum: towards higher catalytic activities empowering sustainable agriculture. J Biomol Struct Dyn 2016; 34:1176–1189 [View Article] [PubMed]
    [Google Scholar]
  10. Cheeseman K, Ropars J, Renault P, Dupont J, Gouzy J et al. Multiple recent horizontal transfers of a large genomic region in cheese making fungi. Nat Commun 2014; 5:2876 [View Article] [PubMed]
    [Google Scholar]
  11. Chen M, Al-lami N, Janvier M, D’Antonio EL, Faraldos JA et al. Mechanistic insights from the binding of substrate and carbocation intermediate analogues to aristolochene synthase. Biochemistry 2013; 52:5441–5453 [View Article] [PubMed]
    [Google Scholar]
  12. Buchvaldt Amby D, Manczak T, Petersen MA, Sundelin T, Weitzel C et al. Role of the Colletotrichum acutatum sesquiterpene synthase CaTPS in the biosynthesis of sesquiterpenoids. Microbiology 2016; 162:1773–1783 [View Article] [PubMed]
    [Google Scholar]
  13. Pinedo C, Wang C-M, Pradier J-M, Dalmais B, Choquer M et al. Sesquiterpene synthase from the botrydial biosynthetic gene cluster of the phytopathogen Botrytis cinerea. ACS Chem Biol 2008; 3:791–801 [View Article] [PubMed]
    [Google Scholar]
  14. Wu W, Tran W, Taatjes CA, Alonso-Gutierrez J, Lee TS et al. Rapid discovery and functional characterization of terpene synthases from four endophytic Xylariaceae. PLoS One 2016; 11:e0146983 [View Article] [PubMed]
    [Google Scholar]
  15. Zhang C, Chen X, Orban A, Shukal S, Birk F et al. Agrocybe aegerita serves as a gateway for identifying sesquiterpene biosynthetic enzymes in higher fungi. ACS Chem Biol 2020; 15:1268–1277 [View Article] [PubMed]
    [Google Scholar]
  16. Engels B, Heinig U, Grothe T, Stadler M, Jennewein S. Cloning and characterization of an Armillaria gallica cDNA encoding protoilludene synthase, which catalyzes the first committed step in the synthesis of antimicrobial melleolides. J Biol Chem 2011; 286:6871–6878 [View Article] [PubMed]
    [Google Scholar]
  17. Wawrzyn GT, Quin MB, Choudhary S, López-Gallego F, Schmidt-Dannert C. Draft genome of Omphalotus olearius provides a predictive framework for sesquiterpenoid natural product biosynthesis in Basidiomycota. Chem Biol 2012; 19:772–783 [View Article] [PubMed]
    [Google Scholar]
  18. Ichinose H, Kitaoka T. Insight into metabolic diversity of the brown-rot basidiomycete Postia placenta responsible for sesquiterpene biosynthesis: semi-comprehensive screening of cytochrome P450 monooxygenase involved in protoilludene metabolism. Microb Biotechnol 2018; 11:952–965 [View Article] [PubMed]
    [Google Scholar]
  19. Nagamine S, Liu C, Nishishita J, Kozaki T, Sogahata K et al. Ascomycete Aspergillus oryzae is an efficient expression host for production of basidiomycete terpenes by using genomic DNA sequences. Appl Environ Microbiol 2019; 85:e00409-19 [View Article] [PubMed]
    [Google Scholar]
  20. Ntana F, Bhat WW, Johnson SR, Jørgensen HJL, Collinge DB et al. A sesquiterpene synthase from the endophytic fungus Serendipita indica catalyzes formation of viridiflorol. Biomolecules 2021; 11:898 [View Article] [PubMed]
    [Google Scholar]
  21. Wu J, Yang X, Duan Y, Wang P, Qi J et al. Biosynthesis of sesquiterpenes in basidiomycetes: a review. J Fungi 2022; 8:913 [View Article] [PubMed]
    [Google Scholar]
  22. Mistry J, Chuguransky S, Williams L, Qureshi M, Salazar GA et al. Pfam: The protein families database in 2021. Nucleic Acids Res 2021; 49:D412–D419 [View Article] [PubMed]
    [Google Scholar]
  23. Khaldi N, Seifuddin FT, Turner G, Haft D, Nierman WC et al. SMURF: Genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol 2010; 47:736–741 [View Article] [PubMed]
    [Google Scholar]
  24. Weber T, Kim HU. The secondary metabolite bioinformatics portal: computational tools to facilitate synthetic biology of secondary metabolite production. Synth Syst Biotechnol 2016; 1:69–79 [View Article] [PubMed]
    [Google Scholar]
  25. Quin MB, Flynn CM, Schmidt-Dannert C. Traversing the fungal terpenome. Nat Prod Rep 2014; 31:1449–1473 [View Article] [PubMed]
    [Google Scholar]
  26. Flynn CM, Schmidt-Dannert C. Sesquiterpene synthase-3-hydroxy-3-methylglutaryl coenzyme a synthase fusion protein responsible for hirsutene biosynthesis in Stereum hirsutum. Appl Environ Microbiol 2018; 84:e00036-18 [View Article] [PubMed]
    [Google Scholar]
  27. Katoh K, Rozewicki J, Yamada KD. MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization. Brief Bioinform 2019; 20:1160–1166 [View Article] [PubMed]
    [Google Scholar]
  28. Galili T. dendextend: an R package for visualizing, adjusting and comparing trees of hierarchical clustering. Bioinformatics 2015; 31:3718–3720 [View Article] [PubMed]
    [Google Scholar]
  29. Vens C, Rosso M-N, Danchin EGJ. Identifying discriminative classification-based motifs in biological sequences. Bioinformatics 2011; 27:1231–1238 [View Article] [PubMed]
    [Google Scholar]
  30. Capella-Gutiérrez S, Silla-Martínez JM, Gabaldón T. trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics 2009; 25:1972–1973 [View Article] [PubMed]
    [Google Scholar]
  31. Mistry J, Finn RD, Eddy SR, Bateman A, Punta M. Challenges in homology search: HMMER3 and convergent evolution of coiled-coil regions. Nucleic Acids Res 2013; 41:e121 [View Article] [PubMed]
    [Google Scholar]
  32. Furukawa J, Morisaki N, Kobayashi H, Iwasaki S, Nozoe S et al. Synthesis of dl-6-protoilludene. Chem Pharm Bull 1985; 33:440–443 [View Article]
    [Google Scholar]
  33. Hage H, Miyauchi S, Virágh M, Drula E, Min B et al. Gene family expansions and transcriptome signatures uncover fungal adaptations to wood decay. Environ Microbiol 2021; 23:5716–5732 [View Article] [PubMed]
    [Google Scholar]
  34. Couillaud J, Amouric A, Courvoisier-Dezord E, Leydet L, Schweitzer N et al. In vitro applications of the terpene mini-path 2.0. Chembiochem 2022; 23:e202200595 [View Article] [PubMed]
    [Google Scholar]
  35. Benedict C. The enzymatic formation of δ-cadinene from farnesyl diphosphate in extracts of cotton. Phytochemistry 1995; 39:327–331 [View Article]
    [Google Scholar]
  36. Zhou Y, Wu C, Dong X, Qu J. Synthesis of 6-trichloromethylphenanthridines by transition metal-free radical cyclization of 2-isocyanobiphenyls. J Org Chem 2016; 81:5202–5208 [View Article] [PubMed]
    [Google Scholar]
  37. Taylor JS, Raes J. Duplication and divergence: the evolution of new genes and old ideas. Annu Rev Genet 2004; 38:615–643 [View Article] [PubMed]
    [Google Scholar]
  38. Garms S, Chen F, Boland W, Gershenzon J, Köllner TG. A single amino acid determines the site of deprotonation in the active center of sesquiterpene synthases SbTPS1 and SbTPS2 from Sorghum bicolor. Phytochemistry 2012; 75:6–13 [View Article] [PubMed]
    [Google Scholar]
  39. Faraldos JA, Miller DJ, González V, Yoosuf-Aly Z, Cascón O et al. A 1,6-ring closure mechanism for (+)-δ-cadinene synthase?. J Am Chem Soc 2012; 134:5900–5908 [View Article] [PubMed]
    [Google Scholar]
  40. Boettger D, Hertweck C. Molecular diversity sculpted by fungal PKS-NRPS hybrids. Chembiochem 2013; 14:28–42 [View Article] [PubMed]
    [Google Scholar]
  41. Tabima JF, Trautman IA, Chang Y, Wang Y, Mondo S et al. Phylogenomic analyses of non-dikarya fungi supports horizontal gene transfer driving diversification of secondary metabolism in the amphibian gastrointestinal symbiont, Basidiobolus. G3 2020; 10:3417–3433 [View Article] [PubMed]
    [Google Scholar]
  42. Koczyk G, Pawłowska J, Muszewska A. Terpenoid biosynthesis dominates among secondary metabolite clusters in Mucoromycotina genomes. J Fungi 2021; 7:285 [View Article] [PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000990
Loading
/content/journal/mgen/10.1099/mgen.0.000990
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error