title: Bioconversion of lovastatin to a novel statin by Amycolatopsis sp.
abstract: 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyzes the conversion of HMG-CoA to mevalonic acid, which plays a significant role in cholesterol synthesis. Several statins, inhibitors of HMG-CoA reductase, can be synthesized and converted by microorganisms. Among 700 strains obtained from culture collections, one strain could convert lovastatin to a novel statin, wuxistatin. The strain was identified as a member of the genus Amycolatopsis based on 16S rRNA gene sequence, morphology analysis, and chemotaxonomic properties. Wuxistatin, a novel HMG-CoA reductase inhibitor, was purified by chromatography, and the structure was determined by electrospray ionization mass and nuclear magnetic resonance spectroscopy. The results show that wuxistatin was butanoic acid, 2-methyl-,1,2,3,5,8,8a-hexahydro-5-hydroxy-7-methyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl) ethy]-1-naphthalenyl ester. An additional hydroxyl group was added to lovastatin at the 5-position to yield wuxistatin. This modification enhanced the intrinsic inhibitory activity (IC50) ofwuxistatin (41+/-5 nM) for fourfold compared with lovastatin (160+/-10 nM). A stoichiometric conversion of lovastatin to wuxistatin occurred.
authors: Key Laboratory of Industrial Biotechnology of the Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, Jiangsu 214122, People's Republic of China.
authors: Bin
authors: B
authors: Zhuge
authors: Hui Ying
authors: HY
authors: Fang
authors: Hai
authors: H
authors: Yu
authors: Zhi Ming
authors: ZM
authors: Rao
authors: Wei
authors: W
authors: Shen
authors: Jian
authors: J
authors: Song
authors: Jian
authors: J
authors: Zhuge
mesh_terms: D000192:Actinomycetales / Q000235:genetics / Q000378:metabolism*; D002087:Butyrates / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin / Q000737:chemistry / Q000378:metabolism*; D012336:RNA, Ribosomal, 16S / Q000032:analysis
chemical_list: D002087:Butyrates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012336:RNA, Ribosomal, 16S; C533002:wuxistatin; D008148:Lovastatin