title: Redesigning alcohol dehydrogenases/reductases for more efficient biosynthesis of enantiopure isomers.
abstract: Alcohol dehydrogenases/reductases predominantly catalyze the asymmetric biosynthesis of optically pure stereoisomers because of their unique chiral constitutions. The enantioselectivities of alcohol dehydrogenases/reductases are substrate- and cofactor-dependent, and therefore they usually catalyze specific reactions with high enantioselectivity under physiological conditions; this may not be suitable for asymmetric biosynthesis with non-natural substrates or non-natural cofactors, and under nonphysiological conditions. It is therefore necessary to modify alcohol dehydrogenases/reductases using various redesigning tools such as directed evolution and rational design, and their combinations, as well as engineering enzyme modules for more efficient production of "non-natural" products. In this article, progress in these aspects of alcohol dehydrogenase/reductase design is reviewed, and future challenges are discussed.
authors: Key Laboratory of Industrial Biotechnology of the Ministry of Education & School of Biotechnology, Jiangnan University, Wuxi 214122, PR China; National Key Laboratory for Food Science, Jiangnan University, Wuxi 214122, PR China.
authors: Rongzhen
authors: R
authors: Zhang
authors: Key Laboratory of Industrial Biotechnology of the Ministry of Education & School of Biotechnology, Jiangnan University, Wuxi 214122, PR China; National Key Laboratory for Food Science, Jiangnan University, Wuxi 214122, PR China. Electronic address: yxu@jiangnan.edu.cn.
authors: Yan
authors: Y
authors: Xu
authors: Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, NJ 08854, USA.
authors: Rong
authors: R
authors: Xiao
mesh_terms: D000426:Alcohol Dehydrogenase / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D002384:Catalysis; D019020:Directed Molecular Evolution; D005818:Genetic Engineering / Q000379:methods / Q000639:trends; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D013237:Stereoisomerism
chemical_list: D000426:Alcohol Dehydrogenase
keywords: Alcohol dehydrogenase/reductase; Chiral biosynthesis; Combination methods; Directed evolution; Enantiopure isomer; Modular engineering; Rational design