Integrative genomic mining for enzyme function to enable engineering of a non-natural biosynthetic pathway

• DOI: 10.1038/ncomms10005
• Publication Date: 2015-11-24T09:59:04Z
• Authors: Wai Shun Mak; Stephen Tran; Ryan Marcheschi; Steve Bertolani; James Thompson; David Baker; James C. Liao; Justin B. Siegel
• Keywords: Protein Engineering; Sequence (biology)

Abstract The ability to biosynthetically produce chemicals beyond what is commonly found in Nature requires the discovery of novel enzyme function. Here we utilize two approaches discover enzymes that enable specific production longer-chain (C 5 –C 8 ) alcohols from sugar. first approach combines bioinformatics and molecular modelling mine sequence databases, resulting a diverse panel capable catalysing targeted reaction. median catalytic efficiency computationally selected 75-fold greater than naively homologues. This integrative genomic mining establishes unique avenue for function rapidly expanding databases. second uses computational design reprogramme specificity. Both result with >100-fold increase specificity When either are integrated vivo , alcohol increases over 10-fold represents >95% total products.