Abstract
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.
Original language | English (US) |
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Pages (from-to) | 1768-1773 |
Number of pages | 6 |
Journal | Beilstein Journal of Organic Chemistry |
Volume | 9 |
DOIs | |
State | Published - Aug 29 2013 |
Externally published | Yes |
Keywords
- Cryptic metabolite
- Dimethyl furan-2,4-dicarboxylate
- Genetic knockout
- Natural products
- Non-ribosomal peptide synthetase module
- Streptomyces
ASJC Scopus subject areas
- Organic Chemistry