Research & Teaching Faculty

Default Header Image

Using substrate engineering to harness enzymatic promiscuity and expand biological catalysis

TitleUsing substrate engineering to harness enzymatic promiscuity and expand biological catalysis
Publication TypeJournal Article
Year of Publication2006
AuthorsLairson, LL, Watts, AG, Wakarchuk, WW, Withers, SG
JournalNATURE CHEMICAL BIOLOGY
Volume2
Pagination724-728
Date PublishedDEC
ISSN1552-4450
Abstract

Despite their unparalleled catalytic prowess and environmental compatibility, enzymes have yet to see widespread application in synthetic chemistry. This lack of application and the resulting underuse of their enormous potential stems not only from a wariness about aqueous biological catalysis on the part of the typical synthetic chemist but also from limitations on enzyme applicability that arise from the high degree of substrate specificity possessed by most enzymes. This latter perceived limitation is being successfully challenged through rational protein engineering(1,2) and directed evolution efforts(3-6) to alter substrate specificity. However, such programs require considerable effort to establish. Here we report an alternative strategy for expanding the substrate specificity, and therefore the synthetic utility, of a given enzyme through a process of `substrate engineering'. The attachment of a readily removable functional group to an alternative glycosyltransferase substrate induces a productive binding mode, facilitating rational control of substrate specificity and regioselectivity using wild-type enzymes.

DOI10.1038/nchembio828