工程改造龟裂链霉菌提高土霉素产量

土霉素是由龟裂链霉菌合成的一类广谱性抗生素，前期研究工作证明其生物合成受其自身途径特异性调控蛋白OtcR的直接调节，OtcR能够激活和促进土霉素合成基因簇的转录表达。在龟裂链霉菌M4018宿主内利用强启动子单独过表达OtcR蛋白，使土霉素的产量提高到原来产量的4倍；为了进一步提高土霉素产量，在M4108宿主内表达乙酰辅酶A羧化酶基因，提高其胞内土霉素合成的前体物丙二酸单酰辅酶A的含量。对出发菌株M4018进行工程改造，同时过表达途径特异性调控蛋白OtcR和乙酰辅酶A羧化酶，发酵检测改造后的重组工程菌株土霉素的产量由1.37g/L提高到9.09g/L，该研究策略对工程改造龟裂链霉菌提高土霉素的产量具有重要的指导意义。

Engineering Strategies for Improved the Oxytetracycline Production in Streptomyces rimosus

Oxytetracycline (OTC) is a broad-spectrum antibiotic produced by Streptomyces rimosus. OtcR was confirmed to be the pathway-specific activator of OTC biosynthesis to directly activate the oxy (oxytetracycline) cluster. OTC production was significantly improved by overexpression of OtcR under the strong promoters. Overexpression of OtcR increased OTC production dramatically by 4 times compared to the parental strain S. rimosus M4018. For a further improvement of the OTC production, the intracellular pool of malonyl-CoA by overexpressing acetyl-CoA carboxylase in M4018 were increased. Herein, for the OTC production, that by overexpressing both the pathway-specific activator OtcR and acetyl-CoA carboxylase in S. rimosus had been shown, a maximum of 9.09g/L was achieved in recombination strains, while only 1.37g/L in the wild type strain M4018.The work has an important significance for engineering industrial strains to improve OTC production.