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A novel L: -isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid.
MedLine Citation:
PMID:  21069315     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
4-Hydroxyisoleucine (HIL) found in fenugreek seeds has insulinotropic and anti-obesity effects and is expected to be a novel orally active drug for insulin-independent diabetes. Here, we show that the newly isolated strain Bacillus thuringiensis 2e2 and the closely related strain B. thuringiensis ATCC 35646 operate a novel metabolic pathway for L: -isoleucine (L: -Ile) via HIL and 2-amino-3-methyl-4-ketopentanoic acid (AMKP). The HIL synthesis was catalyzed stereoselectively by an α-ketoglutaric acid-dependent dioxygenase and to be useful for efficient production of a naturally occurring HIL isomer, (2S,3R,4S)-HIL. The (2S,3R,4S)-HIL was oxidized to (2S,3R)-AMKP by a NAD(+)-dependent dehydrogenase. The metabolic pathway functions as an effective bypass pathway that compensates for the incomplete tricarboxylic acid (TCA) cycle in Bacillus species and also explains how AMKP, a vitamin B(12) antimetabolite with antibiotic activity, is synthesized. These novel findings pave a new way for the commercial production of HIL and also for AMKP.
Authors:
Jun Ogawa; Tomohiro Kodera; Sergey V Smirnov; Makoto Hibi; Natalia N Samsonova; Ryoukichi Koyama; Hiroyuki Yamanaka; Junichi Mano; Takashi Kawashima; Kenzo Yokozeki; Sakayu Shimizu
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Publication Detail:
Type:  Journal Article     Date:  2010-11-11
Journal Detail:
Title:  Applied microbiology and biotechnology     Volume:  89     ISSN:  1432-0614     ISO Abbreviation:  Appl. Microbiol. Biotechnol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406612     Medline TA:  Appl Microbiol Biotechnol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1929-38     Citation Subset:  IM    
Affiliation:
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan, ogawa@kais.kyoto-u.ac.jp.
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