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Non‐natural Cofactor and Formate‐Driven Reductive Carboxylation of Pyruvate
Author(s) -
Guo Xiaojia,
Liu Yuxue,
Wang Qian,
Wang Xueying,
Li Qing,
Liu Wujun,
Zhao Zongbao K.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201915303
Subject(s) - formate , formate dehydrogenase , cofactor , chemistry , carboxylation , pyruvate carboxylase , malic enzyme , combinatorial chemistry , carbon fixation , biochemistry , enzyme , catalysis , dehydrogenase , photosynthesis
A non‐natural cofactor and formate driven system for reductive carboxylation of pyruvate is presented. A formate dehydrogenase (FDH) mutant, FDH*, that favors a non‐natural redox cofactor, nicotinamide cytosine dinucleotide (NCD), for generation of a dedicated reducing equivalent at the expense of formate were acquired. By coupling FDH* and NCD‐dependent malic enzyme (ME*), the successful utilization of formate is demonstrated as both CO 2 source and electron donor for reductive carboxylation of pyruvate with a perfect stoichiometry between formate and malate. When 13 C‐isotope‐labeled formate was used in in vitro trials, up to 53 % of malate had labeled carbon atom. Upon expression of FDH* and ME* in the model host E. coli, the engineered strain produced more malate in the presence of formate and NCD. This work provides an alternative and atom‐economic strategy for CO 2 fixation where formate is used in lieu of CO 2 and offers dedicated reducing power.