Expanding the Substrate Scope of Acyltransferase LovD9 for the Biosynthesis of Statin Analogues

Abstract

This study identifies new acyl donors for manufacturing statin analogues through the acylation of monacolin J acid by the laboratory evolved acyltransferase LovD9. Vinyl and p-nitrophenyl esters have emerged as alternate substrates for LovD9-catalyzed acylation. While vinyl esters can reach product yields as high as the ones obtained by α-dimethyl butyryl-S-methyl-3-mercaptopropionate (DMB-SMMP), the thioester for which LovD9 was evolved, p-nitrophenyl esters display a reactivity even higher than DMB-SMMP for the first acylation step yet the acylation product yield is lower. The reaction mechanisms were elucidated through quantum mechanics (QM) calculations.

Improving statins production: From non‐genetic strategies to genetic strategies

“…[76] Based on the substrate promiscuity of acyltransferase (LovD), more statin deriva-tives can also be obtained by chemically synthesizing different acyl donors. [77] 3…”

“…Designing efficient pathways for acyl donor biosynthesis and engineering LovD based on its substrate specificity and acyl transfer capacity can facilitate the production of diverse statins. [77] S. cerevisiae is an ideal host for heterologous gene expression. [86][87][88] The mature technologies of gene editing and expression, high celldensity culture, and fermentation process control made S. cerevisiae to be a very promising microorganism for statins production.…”