55399-93-4Relevant articles and documents
Engineering Bacillus subtilis Isoleucine Dioxygenase for Efficient Synthesis of (2 S,3 R,4 S)-4-Hydroxyisoleucine
Du, Ping,Pan, Jiang,Qian, Xiao-Long,Xu, Jian-He,Yan, Shuai,Yu, Hui-Lei,Zhang, Zhi-Jun
, p. 14555 - 14563 (2020/12/22)
Isoleucine dioxygenase (IDO)-catalyzed hydroxylation of isoleucine is a promising method for the synthesis of the diabetic drug (2S,3R,4S)-4-hydroxyisoleucine [(2S,3R,4S)-4-HIL]. However, the low activity of IDO significantly limits its practical application. In this work, a high-throughput screening method was developed and directed evolution was performed on the IDO from Bacillus subtilis, resulting in a double mutant with improvements in specific activity, protein expression level, and fermentation titer of 3.2-, 2.8-, and 9.4-fold, respectively. l-Isoleucine (228 mM) was completely converted to (2S,3R,4S)-4-HIL by the best variant with a space-time yield of up to 80.8 g L-1 d-1, which is the highest record reported so far. With a further increase of the substrate loading to 1 M, a high conversion of 91% could also be achieved. At last, enzymatic synthesis of (2S,3R,4S)-4-HIL was successfully carried out on a 3 L scale, indicating tremendous potential of the IDO variant I162T/T182N for green and efficient production of (2S,3R,4S)-4-HIL.
Attempt to simultaneously generate three chiral centers in 4-hydroxyisoleucine with microbial carbonyl reductases
Hibi, Makoto,Takahashi, Koji,Kako, Junko,Wakita, Yuuta,Kodera, Tomohiro,Shimizu, Sakayu,Yokozeki, Kenzo,Ogawa, Jun
, p. 1327 - 1332 (2017/10/05)
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.
An organocatalyzed enantioselective synthesis of (2S,3R,4S)-4- hydroxyisoleucine and its stereoisomers
Kumaraswamy, Gullapalli,Jayaprakash, Neerasa,Sridhar, Balasubramanian
supporting information; experimental part, p. 2745 - 2747 (2010/07/17)
A concise enantioselective total synthesis of (2S,3R,4S)-4- hydroxyisoleucine and its stereoisomers is described. A key feature of this protocol is a catalytic enantioselective mannich reaction that is either anti- or syn-selective as genesis of chirality.
