Bioconversion of lovastatin to a novel statin by Amycolatopsis sp.
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.
Zhuge
Bin
B
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.
Fang
Hui Ying
HY
Yu
Hai
H
Rao
Zhi Ming
ZM
Shen
Wei
W
Song
Jian
J
Zhuge
Jian
J
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
D002087:Butyrates; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012336:RNA, Ribosomal, 16S; C533002:wuxistatin; D008148:Lovastatin