Engineered Streptomyces avermitilis Host for Heterologous Expression of Biosynthetic Gene Cluster for Secondary Metabolites

被引：183

作者：

Komatsu, Mamoru ^{[1
]}

Komatsu, Kyoko ^{[1
]}

Koiwai, Hanae ^{[1
]}

Yamada, Yuuki ^{[1
]}

Kozone, Ikuko ^{[2
]}

Izumikawa, Miho ^{[2
]}

Hashimoto, Junko ^{[2
]}

Takagi, Motoki ^{[2
]}

Omura, Satoshi ^{[3
]}

Shin-ya, Kazuo ^{[4
]}

Cane, David E. ^{[5
]}

Ikeda, Haruo ^{[1
]}

机构：

[1] Kitasato Univ, Kitasato Inst Life Sci, Minami Ku, 1-15-1 Kitasato, Sagamihara, Kanagawa 2520373, Japan

[2] Japan Biol Informat Consortium, Koto Ku, Tokyo 1350064, Japan

[3] Kitasato Univ, Minato Ku, Tokyo 1088641, Japan

[4] Natl Inst Adv Ind Sci & Technol, Koto Ku, Tokyo 1350064, Japan

[5] Brown Univ, Dept Chem, Providence, RI 02912 USA

来源：

ACS SYNTHETIC BIOLOGY | 2013年 / 2卷 / 07期

关键词：

secondary metabolism; heterologous expression; biosynthesis; Streptomyces; genome; COMPLETE GENOME SEQUENCE; POLYKETIDE SYNTHASE; ESCHERICHIA-COLI; FAMILY; PENTALENOLACTONE; IDENTIFICATION; CLAVULIGERUS; DNA; ANTIBIOTICS; RESISTANCE;

D O I：

10.1021/sb3001003

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

An industrial microorganism, Streptomyces avermitilis, which is a producer of anthelmintic macrocyclic lactones, avermectins, has been constructed as a versatile model host for heterologous expression of genes encoding secondary metabolite biosynthesis. Twenty of the entire biosynthetic gene clusters for secondary metabolites were successively cloned and introduced into a versatile model host S. avermitilis SUKA17 or 22. Almost all S. avermitilis transformants carrying the entire gene cluster produced metabolites as a result of the expression of biosynthetic gene clusters introduced. A few transformants were unable to produce metabolites, but their production was restored by the expression of biosynthetic genes using an alternative promoter or the expression of a regulatory gene in the gene cluster that controls the expression of biosynthetic genes in the cluster using an alternative promoter. Production of metabolites in some transformants of the versatile host was higher than that of the original producers, and cryptic biosynthetic gene clusters in the original producer were also expressed in a versatile host.

引用

页码：384 / 396

页数：13

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