Scientific Publications

Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters.

Publication TypeJournal Article
AuthorsCimermancic, P., Medema MH, Claesen J., Kurita K., Wieland Brown LC, Mavrommatis K., Pati A., Godfrey PA, Koehrsen M., Clardy J., Birren BW, Takano E., Sali A., Linington RG, and Fischbach MA
AbstractAlthough biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We experimentally characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1,000 members. Although these clusters are widely divergent in sequence, their small molecule products are remarkably conserved, indicating for the first time the important roles these compounds play in Gram-negative cell biology.
Year of Publication2014
JournalCell
Volume158
Issue2
Pages412-21
Date Published (YYYY/MM/DD)2014/07/17
ISSN Number0092-8674
DOI10.1016/j.cell.2014.06.034
PubMedhttp://www.ncbi.nlm.nih.gov/pubmed/25036635?dopt=Abstract