A biocatalytic platform for asymmetric alkylation of α-keto acids by mining and engineering of methyltransferases.
Nat Commun
; 14(1): 5704, 2023 09 14.
Article
in En
| MEDLINE
| ID: mdl-37709735
ABSTRACT
Catalytic asymmetric α-alkylation of carbonyl compounds represents a long-standing challenge in synthetic organic chemistry. Herein, we advance a dual biocatalytic platform for the efficient asymmetric alkylation of α-keto acids. First, guided by our recently obtained crystal structures, we develop SgvMVAV as a general biocatalyst for the enantioselective methylation, ethylation, allylation and propargylation of a range of α-keto acids with total turnover numbers (TTNs) up to 4,600. Second, we mine a family of bacterial HMTs from Pseudomonas species sharing less than 50% sequence identities with known HMTs and evaluated their activities in SAM regeneration. Our best performing HMT from P. aeruginosa, PaHMT, displays the highest SAM regeneration efficiencies (TTN up to 7,700) among HMTs characterized to date. Together, the synergistic use of SgvMVAV and PaHMT affords a fully biocatalytic protocol for asymmetric methylation featuring a record turnover efficiency, providing a solution to the notorious problem of asymmetric alkylation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Engineering
/
Methyltransferases
Language:
En
Journal:
Nat Commun
Year:
2023
Document type:
Article