A novel L-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid.
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| 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.
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| 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 |
| Journal | Applied microbiology and biotechnology (Appl Microbiol Biotechnol) Vol. 89 Issue 6 Pg. 1929-38 (Mar 2011) ISSN: 1432-0614 [Electronic] Germany |
| PMID | 21069315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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