期刊
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
卷 41, 期 7, 页码 1159-1167出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s10295-014-1449-9
关键词
Saccharopolyspora erythraea; Erythromycin; TetR family transcriptional regulator; SACE_3986; SACE_3985
资金
- National Program on Key Basic Research Project (973 program) [2013CB734000]
- Open Funding Project of the State Key Laboratory of Bioreactor Engineering
- National Natural Science Foundation of China [31300081, 30870069]
- Natural Science Foundation of Anhui Province [1208085MC46]
- Initial Foundation of Doctoral Scientific Research in Anhui University [01001904]
- Youth Foundation of Anhui University [02303305]
Erythromycin, a medically important antibiotic, is produced by Saccharopolyspora erythraea. Unusually, the erythromycin biosynthetic gene cluster lacks a regulatory gene, and the regulation of its biosynthesis remains largely unknown. In this study, through gene deletion, complementation and overexpression experiments, we identified a novel TetR family transcriptional regulator SACE_3986 negatively regulating erythromycin biosynthesis in S. erythraea A226. When SACE_3986 was further inactivated in an industrial strain WB, erythromycin A yield of the mutant was increased by 54.2 % in average compared with that of its parent strain, displaying the universality of SACE_3986 as a repressor for erythromycin production in S. erythraea. qRT-PCR analysis indicated that SACE_3986 repressed the transcription of its adjacent gene SACE_3985 (which encodes a short-chain dehydrogenase/reductase), erythromycin biosynthetic gene eryAI and the resistance gene ermE. As determined by EMSA analysis, purified SACE_3986 protein specifically bound to the intergenic region between SACE_3985 and SACE_3986, whereas it did not bind to the promoter regions of eryAI and ermE. Furthermore, overexpression of SACE_3985 in A226 led to enhanced erythromycin A yield by at least 32.6 %. These findings indicate that SACE_3986 is a negative regulator of erythromycin biosynthesis, and the adjacent gene SACE_3985 is one of its target genes. The present study provides a basis to increase erythromycin production by engineering of SACE_3986 and SACE_3985 in S. erythraea.
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