Abstract
As microbial genome sequencing becomes more widespread, the capacity of microorganisms to produce an immense number of metabolites has come into better view. Utilizing a metabolite/gene cluster correlation platform, the biosynthetic origins of a new family of natural products, the rimosamides, were discovered. The rimosamides were identified in Streptomyces rimosus and associated with their NRPS/PKS-type gene cluster based upon their high frequency of co-occurrence across 179 strains of actinobacteria. This also led to the discovery of the related detoxin gene cluster. The core of each of these families of natural products contains a depsipeptide bond at the point of bifurcation in their unusual branched structures, the origins of which are definitively assigned to nonlinear biosynthetic pathways via heterologous expression in Streptomyces lividans. The rimosamides were found to antagonize the antibiotic activity of blasticidin S against Bacillus cereus.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3452-3460 |
| Number of pages | 9 |
| Journal | ACS chemical biology |
| Volume | 11 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 16 2016 |
Funding
We thank the Agricultural Research Service of the United States Department of Agriculture for providing us bacterial strains. Research reported in this publication was supported by the Northwestern University Department of Chemistry and the National Institutes of Health under award numbers D012016 ACS Chemical Biology Articles (Integrated Molecular Structure Education and Research Center at Northwestern University), GM112739 (F.C.S.), T32-GM008500 (J.A.B.), AT009143 (N.L.K./R.J.T.), and GM077596 (W.W.M.), as well as the NIH supported Chemistry of Life Processes Training Grant T32-GM105538 (R.A.M.).
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine