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Applied and Environmental Microbiology, February 2006, p. 1310-1315, Vol. 72, No. 2
0099-2240/06/$08.00+0     doi:10.1128/AEM.72.2.1310-1315.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Genetic Modification of Bacillus subtilis for Production of D-chiro-Inositol, an Investigational Drug Candidate for Treatment of Type 2 Diabetes and Polycystic Ovary Syndrome

Ken-ichi Yoshida,^1* Masanori Yamaguchi,² Tetsuro Morinaga,¹ Maya Ikeuchi,¹ Masaki Kinehara,¹ and Hitoshi Ashida¹

Department of Biofunctional Chemistry, Faculty of Agriculture, Kobe University, Kobe, Hyogo,¹ Central Research Laboratories, Hokko Chemical Industry Co., Ltd., Atsugi, Kanagawa, Japan²

Received 14 September 2005/ Accepted 21 November 2005

D-chiro-Inositol (DCI) is a drug candidate for the treatment of type 2 diabetes and polycystic ovary syndrome, since it improves the efficiency with which the body uses insulin and also promotes ovulation. Here, we report genetic modification of Bacillus subtilis for production of DCI from myo-inositol (MI). The B. subtilis iolABCDEFGHIJ operon encodes enzymes for the multiple steps of the MI catabolic pathway. In the first and second steps, MI is converted to 2-keto-MI (2KMI) by IolG and then to 3D-(3,5/4)-trihydroxycyclohexane-1,2-dione by IolE. In this study, we identified iolI encoding inosose isomerase, which converts 2KMI to 1-keto-D-chiro-inositol (1KDCI), and found that IolG reduces 1KDCI to DCI. Inactivation of iolE in a mutant constitutively expressing the iol operon blocked the MI catabolic pathway to accumulate 2KMI, which was converted to DCI via the activity of IolI and IolG. The mutant was able to convert at least 6% of input MI in the culture medium to DCI.

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* Corresponding author. Mailing address: Department of Biofunctional Chemistry, Faculty of Agriculture, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan. Phone: 81-78-803-5862. Fax: 81-78-803-5815. E-mail: kenyoshi{at}kobe-u.ac.jp.

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Applied and Environmental Microbiology, February 2006, p. 1310-1315, Vol. 72, No. 2
0099-2240/06/$08.00+0     doi:10.1128/AEM.72.2.1310-1315.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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