Evolutionary repurposing of a sulfatase: A new Michaelis complex leads to efficient transition state charge offset.

ABSTRACT: The recruitment and evolutionary optimization of promiscuous enzymes is key to the rapid adaptation of organisms to changing environments. Our understanding of the precise mechanisms underlying enzyme repurposing is, however, limited: What are the active-site features that enable the molecular recognition of multiple substrates with contrasting catalytic requirements? To gain insights into the molecular determinants of adaptation in promiscuous enzymes, we performed the laboratory evolution of an arylsulfatase to improve its initially weak phenylphosphonate hydrolase activity. The evolutionary trajectory led to a 100,000-fold enhancement of phenylphosphonate hydrolysis, while the native sulfate and promiscuous phosphate mono- and diester hydrolyses were only marginally affected (≤50-fold).

SUBMITTER: Miton CM 

PROVIDER: S-EPMC6077717 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature