In this section
@article{Herbert:2020:10.1002/anie.202004963,
author = {Herbert, AJ and Shepherd, SA and Cronin, VA and Bennett, MR and Sung, R and Micklefield, J},
doi = {10.1002/anie.202004963},
journal = {ANGEWANDTE CHEMIE-INTERNATIONAL EDITION},
pages = {14950--14956},
title = {Engineering Orthogonal Methyltransferases to Create Alternative Bioalkylation Pathways},
url = {http://dx.doi.org/10.1002/anie.202004963},
volume = {59},
year = {2020}
}
TY - JOUR
AB - S-adenosyl-l-methionine (SAM)-dependent methyltransferases (MTs) catalyse the methylation of a vast array of small metabolites and biomacromolecules. Recently, rare carboxymethylation pathways have been discovered, including carboxymethyltransferase enzymes that utilise a carboxy-SAM (cxSAM) cofactor generated from SAM by a cxSAM synthase (CmoA). We show how MT enzymes can utilise cxSAM to catalyse carboxymethylation of tetrahydroisoquinoline (THIQ) and catechol substrates. Site-directed mutagenesis was used to create orthogonal MTs possessing improved catalytic activity and selectivity for cxSAM, with subsequent coupling to CmoA resulting in more efficient and selective carboxymethylation. An enzymatic approach was also developed to generate a previously undescribed co-factor, carboxy-S-adenosyl-l-ethionine (cxSAE), thereby enabling the stereoselective transfer of a chiral 1-carboxyethyl group to the substrate.
AU - Herbert,AJ
AU - Shepherd,SA
AU - Cronin,VA
AU - Bennett,MR
AU - Sung,R
AU - Micklefield,J
DO - 10.1002/anie.202004963
EP - 14956
PY - 2020///
SN - 1433-7851
SP - 14950
TI - Engineering Orthogonal Methyltransferases to Create Alternative Bioalkylation Pathways
T2 - ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
UR - http://dx.doi.org/10.1002/anie.202004963
VL - 59
ER -