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

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논문

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

학술지

Bioorganic & medicinal chemistry

저자명

Hibi, Makoto; Takahashi, Koji; Kako, Junko; Wakita, Yuuta; Kodera, Tomohiro; Shimizu, Sakayu; Yokozeki, Kenzo; Ogawa, Jun

초록

<P><B>Abstract</B></P> <P>A panel of microorganisms was screened for selective reduction ability towards a racemic mixture of prochiral 2-amino-3-methyl-4-ketopentanoate (<I>rac</I>-AMKP). Several of the microorganisms tested produced greater than 0.5mM 4-hydroxyisoleucine (HIL) from <I>rac</I>-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, <I>Ap</I>AR and <I>Fs</I>AR, were identified from two of these microorganisms, <I>Aureobasidium pullulans</I> NBRC 4466 and <I>Fusarium solani</I> TG-2, respectively. Three AMKP reducing enzymes, <I>Ap</I>AR, <I>Fs</I>AR, and the previously reported <I>Bt</I>HILDH, were reacted with <I>rac</I>-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.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

발행연도

2018

발행기관

Elsevier

ISSN

0968-0896

ISSN

1464-3391

26

7

페이지

pp.1327-1332

주제어

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

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논문; 2018-04-01

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