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Title: A novel L-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid.
Authors: Ogawa, Jun  kyouindb  KAKEN_id
Kodera, Tomohiro
Smirnov, Sergey V
Hibi, Makoto  kyouindb  KAKEN_id
Samsonova, Natalia N
Koyama, Ryoukichi
Yamanaka, Hiroyuki
Mano, Junichi
Kawashima, Takashi
Yokozeki, Kenzo
Shimizu, Sakayu
Author's alias: 小川, 順
日比, 慎
Keywords: L-Isoleucine dioxygenase
4-Hydroxyisoleucine
NAD(+)-dependent dehydrogenase
2-Amino-3-methyl-4-ketopentanoic acid
Bacillus thuringiensis
TCA cycle
Issue Date: Mar-2011
Publisher: Springer-Verlag
Journal title: Applied microbiology and biotechnology
Volume: 89
Issue: 6
Start page: 1929
End page: 1938
Abstract: 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.
Rights: The final publication is available at www.springerlink.com
URI: http://hdl.handle.net/2433/139589
DOI(Published Version): 10.1007/s00253-010-2983-7
PubMed ID: 21069315
Appears in Collections:Journal Articles

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