8FTV

SgvM methyltransferase triple variant (M144V/F329V/T331A) with SAH and 2-oxo-4-phenylbutanoic acid

Summary for 8FTV

• Entry DOI: 10.2210/pdb8ftv/pdb
• Related: 8FTR
• Descriptor: Methyltransferase, S-ADENOSYL-L-HOMOCYSTEINE, ZINC ION, ... (5 entities in total)
• Functional Keywords: methyltransferase, biosynthetic protein
• Biological source: Streptomyces griseoviridis
• Total number of polymer chains: 1
• Total formula weight: 37429.35

Authors

Kuzelka, K.,Nair, S.K. (deposition date: 2023-01-13, release date: 2023-11-01)

Primary citation

Ju, S.,Kuzelka, K.P.,Guo, R.,Krohn-Hansen, B.,Wu, J.,Nair, S.K.,Yang, Y.
A biocatalytic platform for asymmetric alkylation of alpha-keto acids by mining and engineering of methyltransferases
Nat Commun, 14:5704-5704, 2023

PubMed 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 SgvM 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 SgvM 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.

PubMed: 37709735
DOI: 10.1038/s41467-023-40980-w

Experimental method

X-RAY DIFFRACTION (2.04 Å)