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Peer-reviewedCC BY 4.0Angewandte Chemie (International Ed. in English)

Nonnative Thiol and Aniline Methylation, Including Enantioselective Dithiol Desymmetrization, by Multicomponent Cobamide‐Dependent Methyltransferases Using Unactivated Methyl Donors

  • Amardeep Kumar1
  • Osman Ishag Adam1
  • Paras Gupta1
  • Jared C. Lewis1
  1. 1Department of Chemistry Indiana University Bloomington Indiana USA
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Abstract

Despite their potential synthetic utility, cobamide‐dependent MTases are relatively underutilized for biocatalysis. We developed mixed MtaABC/MtgABC enzyme platforms capable of catalyzing methylation of non‐native thiol and aniline substrates using unactivated methyl donors like methanol and glycine betaine. This approach allows highly enantioselective and site‐selective methylation of aliphatic thiols with high turnover number (up to 6000), providing the first demonstration of enantioselective non‐native catalysis by cobamide‐dependent enzymes. The MtaAC+MtgB system was subsequently engineered through site‐directed mutagenesis, resulting in large enhancements in activity for the desymmetrization of non‐native ester‐containing prochiral thiols. These findings establish MTase complexes as a promising platform for non‐native biocatalysis.

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Cite

BibTeXRIS
BibTeX
@article{kumar2026nonnative,
  title = {{Nonnative Thiol and Aniline Methylation, Including Enantioselective Dithiol Desymmetrization, by Multicomponent Cobamide‐Dependent Methyltransferases Using Unactivated Methyl Donors}},
  author = {Amardeep Kumar and Osman Ishag Adam and Paras Gupta and Jared C. Lewis},
  journal = {Angewandte Chemie (International Ed. in English)},
  year = {2026},
  month = sep,
  doi = {10.1002/anie.1537547},
  url = {https://doi.org/10.1002/anie.1537547},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Nonnative Thiol and Aniline Methylation, Including Enantioselective Dithiol Desymmetrization, by Multicomponent Cobamide‐Dependent Methyltransferases Using Unactivated Methyl Donors
AU  - Amardeep Kumar
AU  - Osman Ishag Adam
AU  - Paras Gupta
AU  - Jared C. Lewis
PY  - 2026
DA  - 2026/09/16
JO  - Angewandte Chemie (International Ed. in English)
DO  - 10.1002/anie.1537547
UR  - https://doi.org/10.1002/anie.1537547
AB  - Despite their potential synthetic utility, cobamide‐dependent MTases are relatively underutilized for biocatalysis. We developed mixed MtaABC/MtgABC enzyme platforms capable of catalyzing methylation of non‐native thiol and aniline substrates using unactivated methyl donors like methanol and glycine betaine. This approach allows highly enantioselective and site‐selective methylation of aliphatic thiols with high turnover number (up to 6000), providing the first demonstration of enantioselective non‐native catalysis by cobamide‐dependent enzymes. The MtaAC+MtgB system was subsequently engineered through site‐directed mutagenesis, resulting in large enhancements in activity for the desymmetrization of non‐native ester‐containing prochiral thiols. These findings establish MTase complexes as a promising platform for non‐native biocatalysis.
SN  - 1433-7851
SN  - 1521-3773
ER  -