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Abstract Enzymes as catalysts in organic syntheses can provide high regio‐ and stereo‐selectivity, which is often not possible with chemical catalysts. Biocatalysis with iron heme enzymes has proven efficient when the enzyme is sequestered in thin films. An added feature is improved stability. For example, peroxidases chemically crosslinked in poly‐lysine in films on silica nanoparticles were stable for 9 hrs or more at 90 °C, and were used for biocatalysis up to 90 °C. We show here for a series ofpara‐substituted phenols, single nitro‐phenol products can be selectively synthesized using biocatalytic magnetic beads coated with horseradish peroxidase (HRP) crosslinked in polylysine films. Nitrophenols moieties are important as synthetic intermediates and in drugs. For a series ofpara‐substituted phenols, biocatalytic nitration gave average turnover numbers 1.8‐fold larger at 75 °C than at 25 °C. For phenols giving <50 % conversion after 1 hr at 25 °C, twice the nitration yield was achieved in 1 hr at 75 °C. Results indicate that this approach should be valuable as a general tool for biocatalytic chemical synthesis.
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A biocatalytic platform for asymmetric alkylation of α-keto acids by mining and engineering of methyltransferases
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 SgvMVAVas 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 fromPseudomonasspecies sharing less than 50% sequence identities with known HMTs and evaluated their activities in SAM regeneration. Our best performing HMT fromP. aeruginosa,PaHMT, displays the highest SAM regeneration efficiencies (TTN up to 7,700) among HMTs characterized to date. Together, the synergistic use of SgvMVAVandPaHMT affords a fully biocatalytic protocol for asymmetric methylation featuring a record turnover efficiency, providing a solution to the notorious problem of asymmetric alkylation.
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- PAR ID:
- 10480821
- Publisher / Repository:
- Springer
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 14
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript
- Journal Article:
- https://doi.org/10.1038/s41467-023-40980-w
