Controlling Enzymatic Activity by Modulating the Oligomerization State via Chemical Rescue and Optical Control.

ABSTRACT: Selective switching of enzymatic activity has been a longstanding goal in synthetic biology. Drastic changes in activity upon mutational manipulation of the oligomerization state of enzymes have frequently been reported in the literature, but scarcely exploited for switching. Using geranylgeranylglyceryl phosphate synthase as a model, we demonstrate that catalytic activity can be efficiently controlled by exogenous modulation of the association state. We introduced a lysine-to-cysteine mutation, leading to the breakdown of the active hexamer into dimers with impaired catalytic efficiency. Addition of bromoethylamine chemically rescued the enzyme by restoring hexamerization and activity. As an alternative method, we incorporated the photosensitive unnatural amino acid o-nitrobenzyl-O-tyrosi

SUBMITTER: Kropp C 

PROVIDER: S-EPMC9298306 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature