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Cell DOI:10.1016/j.cell.2014.06.034

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

Publication TypeJournal Article
Year of Publication2014
AuthorsCimermancic, P, Medema, MH, Claesen, J, Kurita, K, Brown, LCWieland, Mavrommatis, K, Pati, A, Godfrey, PA, Koehrsen, M, Clardy, J, Birren, BW, Takano, E, Sali, A, Linington, RG, Fischbach, MA
Date Published2014 Jul 17
KeywordsAlgorithms, Bacteria, Mutation, Oxidative Stress, Phylogeny, Secondary Metabolism

Although 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.


Alternate JournalCell
PubMed ID25036635
PubMed Central IDPMC4123684
Grant ListR01 AI101018 / AI / NIAID NIH HHS / United States
DP2 OD007290 / OD / NIH HHS / United States
HHSN272200900018C / AI / NIAID NIH HHS / United States
T32 GM067547 / GM / NIGMS NIH HHS / United States
R21 AI101722 / AI / NIAID NIH HHS / United States
P50 GM081879 / GM / NIGMS NIH HHS / United States
U01 TW006634 / TW / FIC NIH HHS / United States
HHSN272200900018C / / PHS HHS / United States
U19 AI110818 / AI / NIAID NIH HHS / United States