Attempt to simultaneously generate three chiral centers in 4-hydroxyisoleucine with microbial carbonyl reductases

作者：Hibi Makoto; Takahashi Koji; Kako Junko; Wakita Yuuta; Kodera Tomohiro; Shimizu Sakayu; Yokozeki Kenzo; Ogawa Jun^*

来源：Bioorganic & Medicinal Chemistry, 2018, 26(7): 1327-1332.

DOI：10.1016/j.bmc.2017.06.044

• 4-Hydroxyisoleucine
• Stereoisomer
• Carbonyl reductase
• Kinetic resolution
• Asymmetric biosynthesis

A panel of microorganisms was screened for selective reduction ability towards a racemic mixture of prochiral 2-amino-3-methyl-4-ketopentanoate (rac-AMKP). Several of the microorganisms tested produced greater than 0.5 mM 4-hydroxyisoleucine (HIL) from rac-AMKP, and the stereoselectivity of HIL formation was found to depend on the taxonomic category to which the microorganism belonged. The enzymes responsible for the AMKP-reducing activity, ApAR and FsAR, were identified from two of these microorganisms, Aureobasidium pullulans NBRC 4466 and Fusarium solani TG-2, respectively. Three AMKP reducing enzymes, ApAR, FsAR, and the previously reported BtHILDH, were reacted with rac-AMKP, and each enzyme selectively produced a specific composition of HIL stereoisomers. The enzymes appeared to have different characteristics in recognition of the stereostructure of the substrate AMKP and in control of the 4-hydroxyl group configuration in the HIL product.

• 出版日期2018-4-1