Engineering of Dual-Function Vitreoscilla Hemoglobin: A One-Pot Strategy for the Synthesis of Unnatural α-Amino Acids

Fengxi Li; Yaning Xu; Yuelin Xu; Hanqing Xie; Junhao Wu; Chunyu Wang; Zhengqiang Li; Zhi Wang; Lei Wang

doi:10.1021/acs.orglett.3c02537

Engineering of Dual-Function Vitreoscilla Hemoglobin: A One-Pot Strategy for the Synthesis of Unnatural α-Amino Acids

Org Lett. 2023 Oct 6;25(39):7115-7119. doi: 10.1021/acs.orglett.3c02537. Epub 2023 Sep 22.

Authors

Fengxi Li¹, Yaning Xu¹, Yuelin Xu¹, Hanqing Xie¹, Junhao Wu¹, Chunyu Wang², Zhengqiang Li¹, Zhi Wang¹, Lei Wang¹

Affiliations

¹ Key Laboratory of Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, Jilin 130023, P. R. China.
² State Key Laboratory of Supramolecular Structure and Materials, Jilin University, Changchun, Jilin 130023, P. R. China.

PMID: 37737085
DOI: 10.1021/acs.orglett.3c02537

Abstract

Despite a well-developed and growing body of work on the directed evolution of hemoproteins, the potential of hemoproteins to catalyze non-natural reactions remains underexplored. This paper reports a new biocatalytic strategy for the one-pot synthesis of unnatural α-amino acids. Engineered variants of dual-function Vitreoscilla hemoglobin were found to efficiently catalyze N-H insertion and C-H sp³ alkylation, providing moderate to excellent yields (57%-95%) of unnatural α-amino acid derivatives and turnover numbers (1425-2375).