Peptides and methods for carbon-carbon bond formation

Scientists from the Max-Planck-Institute for terrestrial Microbiology explored the biocatalytic potential of the thiamine- diphosphate-dependent (ThDP) oxalyl-CoA decarboxylase (OXC)/2-hydroxyacyl-CoA lyase (HACL) superfamily that naturally catalyzes the shortening of acyl-CoA thioester substrates through the release of the C1-unit formyl-CoA. They showed that the OXC/HACL superfamily contains promiscuous members that can be reversed to perform nucleophilic C1- extensions of various aldehydes to yield the corresponding 2- hydroxyacyl-CoA thioesters. Improved catalytic properties of Methylorubrum extorquens OXC was obtained by enzyme engineering in combination with two newly described enzymes—a specific oxalyl-CoA synthetase and a 2-hydrox- yacyl-CoA thioesterase. This enzymatic cascade enabled continuous conversion of oxalate and aromatic aldehydes into valuable (S)-a-hydroxy acids with enantiomeric excess up to 99 %.

A priority application was filed on 31.08.2019 followed by a PCT application on 29.08.2020.

Burgener, S., Cortina, N. S., & Erb, T. J. (2020). Oxalyl‐CoA Decarboxylase Enables Nucleophilic One‐Carbon Extension of Aldehydes to Chiral α‐Hydroxy Acids. Angewandte Chemie International Edition, 59(14), 5526-5530.