TAR cloning and integrated overexpression of 6-demethylchlortetracycline biosynthetic gene cluster in Streptomyces aureofaciens

被引:16
作者
Wu, Naxin [1 ,2 ]
Huang, He [3 ]
Min, Taoling [2 ]
Hu, Haifeng [2 ]
机构
[1] Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China
[2] Shanghai Inst Pharmaceut Ind, Dept Biopharmceut, Shanghai 201203, Peoples R China
[3] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Plant Physiol & Ecol, Key Lab Synthet Biol, Shanghai 200032, Peoples R China
基金
上海市自然科学基金;
关键词
6-demethylchlortetracycline; Streptomyces aureofaciens; biosynthetic gene cluster; transformation-associated recombination; RECOMBINATION CLONING; SELECTIVE ISOLATION; HETEROLOGOUS EXPRESSION; COMPLEX GENOMES; DNA; BIOLOGY; COLI;
D O I
10.1093/abbs/gmx110
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
6-Demethylchlortetracycline (6-DCT), a tetracycline antibiotic produced by Streptomyces aureofaciens, is a crucial precursor employed for the semi-synthesis of tigecycline, minocycline, and amadacyclin (PTK 0796). In this study, the 6-DCT biosynthetic gene cluster (BGC) was cloned from genomic DNA of a high 6-DCT-producing strain, S. aureofaciens DM-1, using the transformation-associated recombination method. An extra copy of the 6-DCT BGC was introduced and integrated into the chromosome of S. aureofaciens DM-1. Duplication of the 6-DCT BGC resulted in a maximum increase of the 6-DCT titer by 34%.
引用
收藏
页码:1129 / 1134
页数:6
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