☆ 4.7 Article

Uncovering rare NADH-preferring ketol-acid reductoisomerases

METABOLIC ENGINEERING (2014)

期刊

METABOLIC ENGINEERING

卷 26, 期 -, 页码 17-22

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE

DOI: 10.1016/j.ymben.2014.08.003

关键词

Ketol acid reductoisomerase; Cofactor specificity; NADH; NADPH

类别

Biotechnology & Applied Microbiology

资金

Resnick Sustainability Institute (Caltech)
Gordon and Betty Moore Foundation [GBMF2809]

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Protocol

Reagent

摘要

All members of the ketol-acid reductoisomerase (KARI) enzyme family characterized to date have been shown to prefer the nicotinamide adenine dinucleotide phosphate hydride (NADPH) cofactor to nicotinamide adenine dinucleotide hydride (NADH). However, KARIs with the reversed cofactor preference are desirable for industrial applications, including anaerobic fermentation to produce branched-chain amino acids. By applying insights gained from structural and engineering studies of this enzyme family to a comprehensive multiple sequence alignment of KARls, we identified putative NADH-utilizing KARIs and characterized eight whose catalytic efficiencies using NADH were equal to or greater than NADPH. These are the first naturally NADH-preferring KARIs reported and demonstrate that this property has evolved independently multiple times, using strategies unlike those used previously in the laboratory to engineer a KARI cofactor switch. (C) 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved,

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