Discovery of recombinases enables genome mining of cryptic biosynthetic gene clusters in Burkholderiales species

Proceedings of the National Academy of Sciences
2018.0

Abstract

<jats:title>Significance</jats:title> <jats:p>Natural products biosynthesized by cryptic gene clusters represent a largely untapped source for drug discovery. However, mining of these products by promoter engineering is restricted by the lack of streamlined genetic tools, especially in nonmodel biosynthetic gene cluster (BGC)-rich bacteria. Here, we describe the discovery of a pair of bacteriophage recombinases and application of recombinase-assisted promoter engineering to rapidly identify and activate several cryptic biosynthetic gene clusters in two Burkholderiales strains that currently lack effective genetic tools. Construction of an efficient genome engineering platform in a natural product producer expedites mining of cryptic BGCs in their native backgrounds, and host melioration for yield or structure optimization. This strategy enables potentially scalable discovery of novel metabolites with intriguing bioactivities from many other bacteria.

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