Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans

Nature Chemical Biology

Volumn 3, Issue 4, 2007, Pages 213-217

  Bergmann, Sebastian ^a   Schümann, Julia ^a   Scherlach, Kirstin ^a   Lange, Corinna ^a   Brakhage, Axel A ^a,b   Hertweck, Christian ^a,b  

^a HANS KNÖLL INSTITUTE   (Germany)

^b FRIEDRICH SCHILLER UNIVERSITY JENA   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 PYRIDONE DERIVATIVE; ASPYRIDONE A; ASPYRIDONE B; FARINOSONE A; MILITARINONE D; PEPTIDE SYNTHASE; POLYKETIDE SYNTHASE NONRIBOSOMAL PEPTIDE SYNTHETASE; PYRIDONE DERIVATIVE; TENELLIN; UNCLASSIFIED DRUG;

ARTICLE; ASPERGILLUS NIDULANS; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG ISOLATION; DRUG STRUCTURE; DRUG SYNTHESIS; FUNGAL GENETICS; GENOMICS; INFRARED SPECTROSCOPY; MASS SPECTROMETRY; METABOLISM; METABOLITE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; NUCLEOTIDE SEQUENCE; PRIORITY JOURNAL;

EMERICELLA NIDULANS; FUNGI;

ASPERGILLUS NIDULANS; GENES, FUNGAL; GENOME, FUNGAL; MOLECULAR SEQUENCE DATA; MULTIGENE FAMILY; OPEN READING FRAMES; PEPTIDE SYNTHASES; POLYKETIDE SYNTHASES; RECOMBINANT FUSION PROTEINS;

EID: 33947308882     PISSN: 15524450     EISSN: 15524469     Source Type: Journal    
DOI: 10.1038/nchembio869     Document Type: Article

References (34)

1. Van Lanen, S.G. & Shen, B. Microbial genomics for the improvement of natural product discovery. Curr. Opin. Microbiol. 9, 252-260 (2006).
2. Ricke, D.O., Wang, S.W., Cai, R. & Cohen, D. Genomic approaches to drug discovery. Curr. Opin. Chem. Biol. 10, 303-308 (2006).
3. Lautru, S., Deeth, R.J., Bailey, L.M. & Challis, G.L. Discovery of a new peptide natural product by Streptomyces coelicolor genome mining. Nat. Chem. Biol. 1, 265-269 (2005).
4. Peric-Concha, N. & Long, P.F. Mining the microbial metabolome: a new frontier for natural product lead discovery. Drug Discov. Today 8, 1078-1084 (2003).
5. Bode, H.B. & Müller, R. The impact of bacterial genomics on natural product research. Angew. Chem. Int. Ed. 44, 6828-6846 (2005).
6. McAlpine, J.B. et al. Microbial genomics as a guide to drug discovery and structural elucidation: ECO-02301, a novel antifungal agent, as an example. J. Nat. Prod. 68, 493-496 (2005).
7. Scherlach, K. & Hertweck, C. Discovery of aspoquinolones A-D, prenylated quinoline-2-one alkaloids from Aspergillus nidulans, motivated by genome mining. Org. Biomol. Chem. 4, 3517-3520 (2006).
8. Bok, J.W. et al. Genomic mining for Aspergillus natural products. Chem. Biol. 13, 31-37 (2006).
9. Song, L. et al. Type III polyketide synthase β-ketoacyl-ACP starter unit and ethylmalonyl-CoA extender unit selectivity discovered by Streptomyces coelicolor genome mining. J. Am. Chem. Soc. 128, 14754-14755 (2006).
10. Sudek, S., Haygood, M.G., Youssef, D.T. & Schmidt, E.W. Structure of trichamide, a cyclic peptide from the bloom-forming cyanobacterium Trichodesmium erythraeum, predicted from the genome sequence. Appl. Environ. Microbiol. 72, 4382-4387 (2006).
11. Banskota, A.H. et al. Isolation and identification of three new 5-alkenyl-3,3(2H)-furanones from two Streptomyces species using a genomic screening approach. J. Antibiot. (Tokyo) 59, 168-176 (2006).
12. Banskota, A.H. et al. Genomic analyses lead to novel secondary metabolites. Part 3. ECO-0501, a novel antibacterial of a new class. J. Antibiot. (Tokyo) 59, 533-542 (2006).
13. Fazio, G.C., Xu, R. & Matsuda, S.P. Genome mining to identify new plant triterpenoids. J. Am. Chem. Soc. 126, 5678-5679 (2004).
14. Wenzel, S.C. et al. Structure and biosynthesis of myxochromides S1-3 in Stigmatella aurantiaca: evidence for an iterative bacterial type I polyketide synthase and for module skipping in nonribosomal peptide biosynthesis. ChemBioChem 6, 375-380 (2005).
15. Tohyama, S. et al. Genome-inspired search for new antibiotics. Isolation and structure determination of new 28-membered polyketide macrolactones, halstoctacosanolides A and B, from Streptomyces halstedii HC34. Tetrahedron 60, 3999-4005 (2004).
16. Schümann, J. & Hertweck, C. Advances in cloning, functional analysis and heterologous expression of fungal polyketide synthase genes. J. Biotechnol. 124, 690-703 (2006).
17. Galagan, J.E. et al. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438, 1105-1115 (2005).
18. Sims, J.W., Fillmore, J.P., Warner, D.D. & Schmidt, E.W. Equisetin biosynthesis in Fusarium heterosporum. Chem. Commun. (Camb.) 186-188 (2005).
19. Song, Z., Cox, R.J., Lazarus, C.M. & Simpson, T.J. Fusarin C biosynthesis in Fusarium moniliforme and Fusarium venenatum. ChemBioChem 5, 1196-1203 (2004).
20. Dean, R.A. et al. The genome sequence of the rice blast fungus Magnaporthe grisea. Nature 434, 980-986 (2005).
21. Bohnert, H.U. et al. A putative polyketide synthase peptide synthetase from Magnaporthe grisea signals pathogen attack to resistant rice. Plant Cell 16, 2499-2513 (2004).
22. Gaffoor, I. et al. Functional analysis of the polyketide synthase genes in the filamentous fungus Gibberella zeae (Anamorph Fusarium graminearum). Eukaryot. Cell 4, 1926-1933 (2005).
23. Kennedy, J. et al. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284, 1368-1372 (1999).
24. Waring, R.B., May, G.S. & Morris, N.R. Characterization of an inducible expression system in Aspergillus nidulans using alcA and tubulin-coding genes. Gene 79, 119-130 (1989).
25. 13C NMR shifts. A density functional and molecular mechanics study. J. Org. Chem. 61, 8083-8088 (1996).
26. Clark, A.J. & Ellard, J.M. Synthesis of the C9-C25 fragment of L-755,807. Evidence for the relative configuration of the side chain. Tetrahedron Lett. 39, 6033-6036 (1998).
27. Schmidt, K., Riese, U., Li, Z. & Hamburger, M. Novel tetramic acids and pyridone alkaloids, militarinones B, C, and D, from the insect pathogenic fungus Paecilomyces militaris. J. Nat. Prod. 66, 378-383 (2003).
28. McInnes, A.G., Smith, D.G., Wat, C.K., Vining, L.C. & Wright, J.L.C. Tenellin and bassianin, metabolites of Beauveria species - structure elucidation with N-15-enriched and doubly C-13-enriched compounds using C-13 nuclear magnetic-resonance spectroscopy. J. Chem. Soc. Chem. Commun. 281-282 (1974).
29. Cheng, Y. et al. Farinosones A-C, neurotrophic alkaloidal metabolites from the entomogenous deuteromycete Paecilomyces farinosus. J. Nat. Prod. 67, 1854-1858 (2004).
30. Moore, M.C., Cox, R.J., Duffin, G.R. & O'Hagan, D. Synthesis and evaluation of a putative acyl tetramic acid intermediate in tenellin biosynthesis in Beauveria bassiana. A new role for tyrosine. Tetrahedron 54, 9195-9206 (1998).
31. Fujita, Y., Oguri, H. & Oikawa, H. Biosynthetic studies on the antibiotics PF1140: a novel pathway for a 2-pyridone framework. Tetrahedron Lett. 46, 5885-5888 (2005).
32. Lang, G., Blunt, J.W., Cummings, N.J., Cole, A.L. & Munro, M.H.G. Paecilosetin, a new bioactive fungal metabolite from a New Zealand isolate of Paecilomyces farinosus. J. Nat. Prod. 68, 810-811 (2005).
33. Eley, K.L. et al. Biosynthesis of the 2-pyridone tenellin in the insect pathogenic fungus Beauveria bassiana. Chembiochem 8, 289-297 (2007).
34. Herrmann, M., Sprote, P. & Brakhage, A.A. Protein kinase C (PkcA) of Aspergillus nidulans is involved in the penicillin production. Appl. Environ. Microbiol. 72, 2957-2970 (2006).