Cloning and characterization of monacolin K biosynthetic gene cluster from Monascus pilosus

被引:75
作者
Chen, Yi-Pei [1 ,2 ]
Tseng, Ching-Ping [2 ]
Liaw, Li-Ling [1 ]
Wang, Chun-Lin [1 ]
Chen, I-Ching [1 ]
Wu, Wen-Jung [1 ]
Wu, Ming-Der [1 ]
Yuan, Gwo-Fang [1 ]
机构
[1] Food Ind Res & Dev Inst, Bioresource Collect & Res Ctr, Hsinchu, Taiwan
[2] Natl Chiao Tung Univ, Dept Biol Sci & Technol, Hsinchu, Taiwan
关键词
monacolin K; polyketide synthases; Monascus pilosus; bacterial artificial chromosome;
D O I
10.1021/jf800595k
中图分类号
S [农业科学];
学科分类号
09 ;
摘要
Monacolin K is a secondary metabolite synthesized by polyketide synthases (PKS) from Monascus, and it has the same structure as lovastatin, which is mainly produced by Aspergillus terreus. In the present study, a bacterial artificial chromosome (BAC) clone, mps01, was screened from the BAC library constructed from Monascus pilosus BCRC38072 genomic DNA. The putative monacolin K biosynthetic gene cluster was found within a 42 kb region in the mps01 clone. The deduced amino acid sequences encoded by the nine genes designated as mokA-mokl, which share over 54% similarity with the lovastatin biosynthetic gene cluster in A. terreus, were assumed to be involved in monacolin K biosynthesis. A gene disruption construct designed to replace the central part of mokA, a polyketide synthase gene, in wild-type M. pilosus BCRC38072 with a hygromycin B resistance gene through homologous recombination, resulted in a mokA-disrupted strain. The disruptant did not produce monacolin K, indicating that mokA encoded the PKS responsible for monacolin K biosynthesis in M. pilosus BCRC38072.
引用
收藏
页码:5639 / 5646
页数:8
相关论文
共 24 条
[21]   Polyketide synthase gene responsible for citrinin biosynthesis in Monascus purpureus [J].
Shimizu, T ;
Kinoshita, H ;
Ishihara, S ;
Sakai, K ;
Nagai, S ;
Nihira, T .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2005, 71 (07) :3453-3457
[22]   Transformations of cyclic nonaketides by Aspergillus terreus mutants blocked for lovastatin biosynthesis at the lovA and lovC genes [J].
Sorensen, JL ;
Auclair, K ;
Kennedy, J ;
Hutchinson, CR ;
Vederas, JC .
ORGANIC & BIOMOLECULAR CHEMISTRY, 2003, 1 (01) :50-59
[23]   Monacolin N, a compound resulting from derailment of type I iterative polyketide synthase function en route to lovastatin [J].
Sorensen, JL ;
Vederas, JC .
CHEMICAL COMMUNICATIONS, 2003, (13) :1492-1493
[24]   Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors [J].
Tobert, JA .
NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (07) :517-526