Discovery of a new peptide natural product by Streptomyces coelicolor genome mining - PubMed (original) (raw)

doi: 10.1038/nchembio731. Epub 2005 Sep 11.

Affiliations

PMID: 16408055
DOI: 10.1038/nchembio731

Discovery of a new peptide natural product by Streptomyces coelicolor genome mining

Sylvie Lautru et al. Nat Chem Biol. 2005 Oct.

Abstract

Analyses of microbial genome sequences reveal numerous examples of gene clusters encoding proteins typically involved in complex natural product biosynthesis but not associated with the production of known natural products. In Streptomyces coelicolor M145 there are several gene clusters encoding new nonribosomal peptide synthetase (NRPS) systems not associated with known metabolites. Application of structure-based models for substrate recognition by NRPS adenylation domains predicts the amino acids incorporated into the putative peptide products of these systems, but the accuracy of these predictions is untested. Here we report the isolation and structure determination of the new tris-hydroxamate tetrapeptide iron chelator coelichelin from S. coelicolor using a genome mining approach guided by substrate predictions for the trimodular NRPS CchH, and we show that this enzyme, which lacks a C-terminal thioesterase domain, together with a homolog of enterobactin esterase (CchJ), are required for coelichelin biosynthesis. These results demonstrate that accurate prediction of adenylation domain substrate selectivity is possible and raise intriguing mechanistic questions regarding the assembly of a tetrapeptide by a trimodular NRPS.

PubMed Disclaimer

Comment in

Decoding chemical structures from genomes.
Bachmann BO. Bachmann BO. Nat Chem Biol. 2005 Oct;1(5):244-5. doi: 10.1038/nchembio1005-244. Nat Chem Biol. 2005. PMID: 16408048 No abstract available.

Cited by

Multiplexed metagenome mining using short DNA sequence tags facilitates targeted discovery of epoxyketone proteasome inhibitors.
Owen JG, Charlop-Powers Z, Smith AG, Ternei MA, Calle PY, Reddy BV, Montiel D, Brady SF. Owen JG, et al. Proc Natl Acad Sci U S A. 2015 Apr 7;112(14):4221-6. doi: 10.1073/pnas.1501124112. Epub 2015 Mar 23. Proc Natl Acad Sci U S A. 2015. PMID: 25831524 Free PMC article.
Mini review: Genome mining approaches for the identification of secondary metabolite biosynthetic gene clusters in Streptomyces.
Lee N, Hwang S, Kim J, Cho S, Palsson B, Cho BK. Lee N, et al. Comput Struct Biotechnol J. 2020 Jun 21;18:1548-1556. doi: 10.1016/j.csbj.2020.06.024. eCollection 2020. Comput Struct Biotechnol J. 2020. PMID: 32637051 Free PMC article. Review.
Proteomics guided discovery of flavopeptins: anti-proliferative aldehydes synthesized by a reductase domain-containing non-ribosomal peptide synthetase.
Chen Y, McClure RA, Zheng Y, Thomson RJ, Kelleher NL. Chen Y, et al. J Am Chem Soc. 2013 Jul 17;135(28):10449-56. doi: 10.1021/ja4031193. Epub 2013 Jul 2. J Am Chem Soc. 2013. PMID: 23763305 Free PMC article.
Genomic basis for natural product biosynthetic diversity in the actinomycetes.
Nett M, Ikeda H, Moore BS. Nett M, et al. Nat Prod Rep. 2009 Nov;26(11):1362-84. doi: 10.1039/b817069j. Epub 2009 Sep 1. Nat Prod Rep. 2009. PMID: 19844637 Free PMC article. Review.
Co-elicitation of lignocelluloytic enzymatic activities and metabolites production in an Aspergillus-Streptomyces co-culture during lignocellulose fractionation.
Detain J, Rémond C, Rodrigues CM, Harakat D, Besaury L. Detain J, et al. Curr Res Microb Sci. 2022 Feb 11;3:100108. doi: 10.1016/j.crmicr.2022.100108. eCollection 2022. Curr Res Microb Sci. 2022. PMID: 35243445 Free PMC article.

Discovery of a new peptide natural product by Streptomyces coelicolor genome mining - PubMed (original) (raw)