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
作者： Ken-ichi Yoshida , Masanori Yamaguchi , Tetsuro Morinaga , Maya Ikeuchi , Masaki Kinehara
DOI: 10.1128/AEM.72.2.1310-1315.2006
关键词:
摘要: d-chiro-Inositol (DCI) is a drug candidate for the treatment of type 2 diabetes and polycystic ovary syndrome, since it improves efficiency with which body uses insulin also promotes ovulation. Here, we report genetic modification Bacillus subtilis production DCI from myo-inositol (MI). The B. iolABCDEFGHIJ operon encodes enzymes multiple steps MI catabolic pathway. In first second steps, converted to 2-keto-MI (2KMI) by IolG then 3d-(3,5/4)-trihydroxycyclohexane-1,2-dione IolE. this study, identified iolI encoding inosose isomerase, converts 2KMI 1-keto-d-chiro-inositol (1KDCI), found that reduces 1KDCI DCI. Inactivation iolE in mutant constitutively expressing iol blocked pathway accumulate 2KMI, was via activity IolI IolG. able convert at least 6% input culture medium
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