A systematic computational analysis of biosynthetic gene cluster evolution: lessons for engineering biosynthesis.

ABSTRACT: Bacterial secondary metabolites are widely used as antibiotics, anticancer drugs, insecticides and food additives. Attempts to engineer their biosynthetic gene clusters (BGCs) to produce unnatural metabolites with improved properties are often frustrated by the unpredictability and complexity of the enzymes that synthesize these molecules, suggesting that genetic changes within BGCs are limited by specific constraints. Here, by performing a systematic computational analysis of BGC evolution, we derive evidence for three findings that shed light on the ways in which, despite these constraints, nature successfully invents new molecules: 1) BGCs for complex molecules often evolve through the successive merger of smaller sub-clusters, which function as independent evolutionary entities. 2) An

SUBMITTER: Medema MH 

PROVIDER: S-EPMC4256081 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature