Method for improving erythrocin yield through inactivation saccharopolyspora erythraea SACE_3446 gene

Abstract

The invention discloses a method for improving erythrocin yield through a negative control gene SACE_3446 on an inactivation saccharopolyspora erythraea chromosome. Saccharopolyspora erythraea is used for producing erythrocin. The erythrocin and derived drugs of the erythrocin such as clarithromycin, azithromycin and telithromycin are used widely in clinic. Erythrocin high-producing strain screening is very important in industrial production. The erythromycin biosynthesis negative control gene SACE_3446 is screened from a saccharopolyspora erythraea TetR family. Compared with erythrocin yield of an original strain, deletion mutants of the saccharopolyspora erythraea SACE_3446 is improved remarkably, the erythrocin is returned to low yield after gene complementation of the SACE_3446, and therefore the SACE_3446 gene is a erythromycin biosynthesis negative control gene. The inactivation saccharopolyspora erythraea SACE_3446 gene can improve the erythrocin yield through a genetic engineering way. Due to the fact that erythromycin biosynthesis gene control is a network system, upstream and downstream control factors acted by SACE_3446 control factors can be found by using the SACE_3446 as an object. The erythrocin yield can also be improved by changing upstream or downstream control factor genes of the saccharopolyspora erythraea SACE_3446 control factors.

Description

technical field [0001] The invention belongs to the technical field of genetic engineering, and specifically constructs a genetic engineering strain by inactivating or deleting the erythromycin biosynthesis negative regulation gene SACE_3446 on the chromosome of Erythromycetes saccharopolyspora, and improves the yield of erythromycin by fermentation. Background technique [0002] Secondary metabolites of actinomycetes have a wide range of uses, such as antibiotics, anticancer agents, immunomodulators, anthelmintics, insect control agents [1,2]. Among the 23,000 biologically active secondary metabolites discovered so far, more than 10,000 are produced by actinomycetes. However, the original production of these secondary metabolites is very low, and screening is required to obtain high-yielding strains for industrial production. In the past, industrial strains were mainly obtained by random physical or chemical mutagenesis [3,4]. Traditional random mutagenesis techniques ar...

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In 2007, Oliynyk et al. [7] reported the genome sequence of S. ...

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