Activation of cryptic metabolite production through gene disruption: Dimethyl furan-2,4-dicarboxylate produced by Streptomyces sahachiroi

Autor: Dinesh Simkhada, Huitu Zhang, Shogo Mori, Howard Williams, Coran M. H. Watanabe
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Beilstein Journal of Organic Chemistry, Vol 9, Iss 1, Pp 1768-1773 (2013)
Druh dokumentu: article
ISSN: 1860-5397
DOI: 10.3762/bjoc.9.205
Popis: At least 65% of all small molecule drugs on the market today are natural products, however, re-isolation of previously identified and characterized compounds has become a serious impediment to the discovery of new bioactive natural products. Here, genetic knockout of an unusual non-ribosomal peptide synthetase (NRPS) C-PCP-C module, aziA2, is performed resulting in the accumulation of the secondary metabolite, dimethyl furan-2,4-dicarboxylate. The cryptic metabolite represents the first non-azinomycin related compound to be isolated and characterized from the soil bacterium, S. sahachiroi. The results from this study suggest that abolishing production of otherwise predominant natural products through genetic knockout may constitute a means to “activate” the production of novel secondary metabolites that would otherwise lay dormant within microbial genome sequences.
Databáze: Directory of Open Access Journals