CLONING, CHARACTERIZATION AND EXPRESSION OF THE GENE ENCODING CYTOCHROME P-450(SCA-2) FROM STREPTOMYCES-CARBOPHILUS INVOLVED IN PRODUCTION OF PRAVASTATIN, A SPECIFIC HMG-COA REDUCTASE INHIBITOR

被引：56

作者：

WATANABE, I

NARA, F

SERIZAWA, N

机构：

[1] SANKYO CO LTD,BIOMED RES LABS,SHINJUKU KU,TOKYO 140,JAPAN

[2] SANKYO CO LTD,BIOL RES LABS,SHINJUKU KU,TOKYO 140,JAPAN

来源：

GENE | 1995年 / 163卷 / 01期

关键词：

HYPERCHOLESTEROLEMIA; RECOMBINANT DNA; INDUCTION; NORTHERN BLOT ANALYSIS; ACTINOMYCETES;

D O I：

10.1016/0378-1119(95)00394-L

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Pravastatin, a drug for treating hypercholesterolemia, is produced by hydroxylation of ML-236B . Na in Streptomyces carbophilus (Sc) catalyzed by the cytochrome P-450(sca) (CytP-450(sca)) monooxygenase system. The gene (cytP-450(sca-2)) encoding CytP-450(sca-2) was cloned from Sc. The gene had an open reading frame of 1233 bp, encoding a 410-amino-acid protein. The partial sequencing of the purified CytP-450(sca-2) revealed that the N-terminal Met had been removed. CytP-450(sca-2) contained the heme-binding HR2 region characteristic of all CytP-450, as well as the putative oxygen-binding site proposed in CytP-450(cam) from Pseudomonas putida. ML-236B . Na enhanced transcription of cytP-450(sca-2), suggesting that substrate induction in Sc is transcriptionally regulated. S. lividans (Sl) transfected with cytP-450(sca-2) converted ML-236B . Na to pravastatin, indicating the cloned gene to be functional in Sl.

引用

页码：81 / 85

页数：5

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