title: Establishing a Mathematical Equations and Improving the Production of L-tert-Leucine by Uniform Design and Regression Analysis.
abstract: L-tert-Leucine (L-Tle) and its derivatives are extensively used as crucial building blocks for chiral auxiliaries, pharmaceutically active ingredients, and ligands. Combining with formate dehydrogenase (FDH) for regenerating the expensive coenzyme NADH, leucine dehydrogenase (LeuDH) is continually used for synthesizing L-Tle from α-keto acid. A multilevel factorial experimental design was executed for research of this system. In this work, an efficient optimization method for improving the productivity of L-Tle was developed. And the mathematical model between different fermentation conditions and L-Tle yield was also determined in the form of the equation by using uniform design and regression analysis. The multivariate regression equation was conveniently implemented in water, with a space time yield of 505.9 g L-1day-1and an enantiomeric excess value of >99 %. These results demonstrated that this method might become an ideal protocol for industrial production of chiral compounds and unnatural amino acids such as chiral drug intermediates.
authors.affiliation: Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.|The Key Lab for Synthetic Biotechnology of Xiamen City, Xiamen University, Xiamen, 361005, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.|The Key Lab for Synthetic Biotechnology of Xiamen City, Xiamen University, Xiamen, 361005, China.
authors.forename: Chao-Zhen
authors.initials: CZ
authors.lastname: Xu
authors.affiliation: Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
authors.forename: Si-Zhi
authors.initials: SZ
authors.lastname: Jiang
authors.affiliation: Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
authors.forename: Tang-Duo
authors.initials: TD
authors.lastname: Zhang
authors.affiliation: Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China.
authors.forename: Shi-Zhen
authors.initials: SZ
authors.lastname: Wang
authors.affiliation: Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China. fbs@xmu.edu.cn.|The Key Lab for Synthetic Biotechnology of Xiamen City, Xiamen University, Xiamen, 361005, China. fbs@xmu.edu.cn.|The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian, 361005, China. fbs@xmu.edu.cn.
authors.forename: Bai-Shan
authors.initials: BS
authors.lastname: Fang
mesh_terms: D000586:Amination; D001709:Biotechnology / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005560:Formate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D005818:Genetic Engineering; D007930:Leucine / Q000096:biosynthesis* / Q000737:chemistry / Q000031:analogs & derivatives; D050803:Leucine Dehydrogenase / Q000235:genetics / Q000378:metabolism; D008962:Models, Theoretical; D019289:Pyruvic Acid / Q000737:chemistry / Q000378:metabolism; D012044:Regression Analysis; D014633:Valine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry
chemical_list: C089871:2-amino-3,3-dimethylbutanoic acid; D019289:Pyruvic Acid; D005560:Formate Dehydrogenases; D050803:Leucine Dehydrogenase; D007930:Leucine; D014633:Valine
keywords: Biocatalysis; Chiral drug intermediate; Experimental design; L-tert-Leucine; Uniform design