Conversion of cyclic nonaketides to lovastatin and compactin by a lovC deficient mutant of Aspergillus terreus

被引：28

作者：

Auclair, K

Kennedy, J

Hutchinson, CR

Vederas, JC ^{[1
]}

机构：

[1] Univ Alberta, Dept Chem, Edmonton, AB T6G 2G2, Canada

[2] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA

[3] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA

[4] Kosan Biosci Inc, Hayward, CA 94545 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 12期

基金：

美国国家卫生研究院; 加拿大自然科学与工程研究理事会;

关键词：

D O I：

10.1016/S0960-894X(01)00290-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Investigation of the post-PKS biosynthetic steps to the cholesterol-lowering agent lovastatin (1) using an Aspergillus terreus strain with a disrupted lovC gene, which is essential for formation of 4a,5-dihydromonacolin L (3), shows that 7 and 3 are precursors to 1, and demonstrates that lovastatin diketide synthase (lovF protein) does not require lovC. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：1527 / 1531

页数：5

相关论文

共 23 条

[1] MEVINOLIN - A HIGHLY POTENT COMPETITIVE INHIBITOR OF HYDROXYMETHYLGLUTARYL-COENZYME-A REDUCTASE AND A CHOLESTEROL-LOWERING AGENT [J].

ALBERTS, AW ;

CHEN, J ;

KURON, G ;

HUNT, V ;

HUFF, J ;

HOFFMAN, C ;

ROTHROCK, J ;

LOPEZ, M ;

JOSHUA, H ;

HARRIS, E ;

PATCHETT, A ;

MONAGHAN, R ;

CURRIE, S ;

STAPLEY, E ;

ALBERSSCHONBERG, G ;

HENSENS, O ;

HIRSHFIELD, J ;

HOOGSTEEN, K ;

LIESCH, J ;

SPRINGER, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1980, 77 (07) :3957-3961

[2] CRYSTAL AND MOLECULAR-STRUCTURE OF COMPACTIN, A NEW ANTIFUNGAL METABOLITE FROM PENICILLIUM-BREVICOMPACTUM [J].

BROWN, AG ;

SMALE, TC ;

KING, TJ ;

HASENKAMP, R ;

THOMPSON, RH .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1976, (11) :1165-1173

[3]

BROWN MS, 1978, J BIOL CHEM, V253, P1121

[4] DIHYDROMONACOLIN-L AND MONACOLIN-X, NEW METABOLITES THOSE INHIBIT CHOLESTEROL-BIOSYNTHESIS [J].

ENDO, A ;

HASUMI, K ;

NAKAMURA, T ;

KUNISHIMA, M ;

MASUDA, M .

JOURNAL OF ANTIBIOTICS, 1985, 38 (03) :321-327

[5] BIOSYNTHESIS OF ML-236B (COMPACTIN) AND MONACOLIN-K [J].

ENDO, A ;

NEGISHI, Y ;

IWASHITA, T ;

MIZUKAWA, K ;

HIRAMA, M .

JOURNAL OF ANTIBIOTICS, 1985, 38 (03) :444-448

[6] HMG-COA REDUCTASE INHIBITORS [J].

ENDO, A ;

HASUMI, K .

NATURAL PRODUCT REPORTS, 1993, 10 (06) :541-550

[7] MONACOLIN-K, A NEW HYPOCHOLESTEROLEMIC AGENT PRODUCED BY A MONASCUS SPECIES [J].

ENDO, A .

JOURNAL OF ANTIBIOTICS, 1979, 32 (08) :852-854

[8] ML-236A, ML-236B, AND ML-236C, NEW INHIBITORS OF CHOLESTEROGENESIS PRODUCED BY PENICILLIUM CITRINUM [J].

ENDO, A ;

KURODA, M ;

TSUJITA, Y .

JOURNAL OF ANTIBIOTICS, 1976, 29 (12) :1346-1348

[9] COMPACTIN (ML-236B) AND RELATED-COMPOUNDS AS POTENTIAL CHOLESTEROL-LOWERING AGENTS THAT INHIBIT HMG-COA REDUCTASE [J].

ENDO, A .

JOURNAL OF MEDICINAL CHEMISTRY, 1985, 28 (04) :401-405

[10] MEVINOLINIC ACID BIOSYNTHESIS BY ASPERGILLUS-TERREUS AND ITS RELATIONSHIP TO FATTY-ACID BIOSYNTHESIS [J].

GREENSPAN, MD ;

YUDKOVITZ, JB .

JOURNAL OF BACTERIOLOGY, 1985, 162 (02) :704-707