Biocatalytic synthesis of non-standard amino acids by a decarboxylative aldol reaction.

ABSTRACT: Enzymes are renowned for their catalytic efficiency and selectivity. Despite the wealth of carbon-carbon bond forming transformations in traditional organic chemistry and nature, relatively few C-C bond forming enzymes have found their way into the biocatalysis toolbox. Here we show that the enzyme UstD performs a highly selective decarboxylative aldol addition with diverse aldehyde substrates to make non-standard, γ-hydroxy amino acids. We increased the activity of UstD through three rounds of classic directed evolution and an additional round of computationally-guided engineering. The enzyme that emerged, UstD^v2.0, is efficient in a whole-cell biocatalysis format. The products are highly desirable, functionally rich bioactive γ-hydroxy amino acids that we demonstrate can be pr

SUBMITTER: Ellis JM 

PROVIDER: S-EPMC9355265 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature