Characterization of a novel cytochrome P450 from Amycolatopsis sp. CGMCC1149 for hydroxylation of lovastatin

  title={Characterization of a novel cytochrome P450 from Amycolatopsis sp. CGMCC1149 for hydroxylation of lovastatin},
  author={H. Zong and B. Zhuge and Xinyao Lu and X. Huo and H. Fang and Jian Song and J. Sun},
  journal={Biotechnology and Applied Biochemistry},
  • H. Zong, B. Zhuge, +4 authors J. Sun
  • Published 2015
  • Biology, Medicine
  • Biotechnology and Applied Biochemistry
Wuxistatin, a novel and potent statin, is converted from lovastatin by Amycolatopsis sp. CGMCC1149. In the bioconversion, lovastatin is firstly hydroxylated to 3‐hydroxymethyl lovastatin (product I) by a hydroxylase. In the current study, a novel hydroxylase gene p450lov was isolated from Amycolatopsis sp. CGMCC1149 by degenerate PCR and self‐formed adaptor PCR and expressed in Escherichia coli. The gene encodes a 403‐amino‐acid protein with a molecular weight of 44.8 kDa and was designated as… Expand
Secondary Metabolites of the Genus Amycolatopsis: Structures, Bioactivities and Biosynthesis
The objective in this review is to summarize the chemical structures and biological activities of secondary metabolites from the genus Amycolatopsis, a rare actinomycete genus with the potential to produce antibiotics with a total of 159 compounds derived from 8 known and 18 unidentified species. Expand
Detection of 4a,5-dihydropravastatin as Impurity in the Cholesterol Lowering Drug Pravastatin
In fermentation broth samples of the single step production of pravastatin, 4a,5-dihydro analogues are detected and identified for the first time and it is confirmed that after several recrystallization steps this impurity can be fully removed from the pravastsatin powder. Expand


Advances in the bioconversion mechanism of lovastatin to wuxistatin by Amycolatopsis sp. CGMCC 1149
Hydroxylation reaction established in a cell-free system could be inhibited by CO and enhanced by ATP, Fe2+, and ascorbic acid, which were consistent with the presumption that the hydroxylase was an induced cytochrome P450. Expand
Bioconversion of lovastatin to a novel statin by Amycolatopsis sp.
Abstract3-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,Expand
Cloning and heterologous expression of P450Um-1, a novel bacterial P450 gene, for hydroxylation of immunosuppressive agent AS1387392
Results show that P450Um-1, a novel bacterial P450, catalyzed hydroxylation of AS1387392 to AS1429716, and this resultant recombinant strain is expected to be an efficient biocatalyst with application to more suitable redox systems than those tested here. Expand
Cytochrome P450105D1 (CYP105D1) from Streptomyces griseus: heterologous expression, activity, and activation effects of multiple xenobiotics.
The open reading frame of CYP105D1, a soluble cytochrome P450 from Streptomyces griseus, was cloned behind the tac promoter of the bacterial expression vector pSPg1910L and expressed in Escherichia coli, producing an alternative to whole-cell biotransformation of xenobiotic for the production of drug metabolites and an experimental system for probing the structural features of a cyto chrome P450 with a broad substrate range. Expand
Bioconversion of compactin to pravastatin by Actinomadura sp. ATCC 55678
Abstract The screening of known and unidentified actinomycetes revealed three strains which could hydroxylate compactin to pravastatin. The best was a new culture identified as Actinomadura sp. (ATCCExpand
Crystal Structures of Cytochrome P450 105P1 from Streptomyces avermitilis: Conformational Flexibility and Histidine Ligation State
The H72A mutant showed spectroscopic characteristics that were almost identical to those of the wild-type protein, and the highly flexible feature of the BC loop region of CYP105P1 may be required to accept a large hydrophobic substrate. Expand
Cloning, characterization and expression of the gene encoding cytochrome P-450sca-in2 from Streptomyces carbophilus involved in production of pravastatin, a specific HMG-CoA reductase inhibitor
Pravastatin enhanced transcription of cytP -450 sca-2 , suggesting that substrate induction in Sc is transcriptionally regulated, and the cloned gene to be functional in Sl. Expand
Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent.
  • A. Alberts, J. Chen, +17 authors J. Springer
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1980
It was shown that mevinolin was an orally active cholesterol-lowering agent in the dog and orally administered sodium mevinolinate was an active inhibitor of cholesterol synthesis in an acute assay. Expand
Coexpression in yeast of Taxus cytochrome P450 reductase with cytochrome P450 oxygenases involved in Taxol biosynthesis.
Functional transgenic coupling of the Taxus reductase with a homologous cytochrome P450 taxoid hydroxylase represents an important initial step in reconstructing Taxol biosynthesis in a microbial host. Expand
Preliminary crystallographic analysis of an enzyme involved in erythromycin biosynthesis: Cytochrome P450eryF
Cytochrome P450eryF was overexpressed in Escherichia coli and purified in high yield and anomalous dispersion difference Patterson maps have revealed the location of the single heme iron atom. Expand