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Improvement of milbemycin-producing Streptomyces bingchenggensis by rational screening of ultraviolet- and chemically induced mutants

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Abstract

Milbemycin antibiotics are produced by Streptomyces hygroscopicus subsp. aureolacrimosus and a newly isolated Streptomyces bingchenggensis, respectively. According to the biosynthetic pathway of milbemycins generated by S. hygroscopicus subsp. aureolacrimosus, a rational screening procedure with UV irradiation and N-methyl-N′-nitroso-N-nitrosoguanidine (NTG) mutation was performed to obtain high milbemycin-producing S. bingchenggensis. Aminoacetic acid (Glycine)-resistant mutants (AAr), propionate-resistant mutants (PRPr), streptomycin-resistant mutants (STRr) and 2-deoxy-d-glucose-resistant mutants (DOGr) were selected successively. A strain S. bingchenggensis BC-109-6 with AAr, PRPr, STRr and DOGr was obtained and its production of milbemycin A3 and A4 reached 1,450 μg/ml, which was 80% higher than that of the ancestral strain S. bingchenggensis BC-101-4. The subculture experiments indicated that the hereditary characteristic of high productivity of S. bingchenggensis BC-109-6 was stable. The production of milbemycin A3 and A4 by S. bingchenggensis BC-109-6 in a 50-l fermentor could reach 1,380 μg/ml after 360 h batch fermentation.

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Acknowledgment

This study was financially supported by the National Key Technology R&D Program (No. 2006BAD31B02), the National Natural Science Foundation of China (30571234 and 30771427), and the Outstanding Youth Foundation of Heilongjiang Province (No. JC200706).

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  1. School of Life Science, Northeast Agricultural University, 150030, Harbin, China

    Xiang-Jing Wang, Xiao-Chong Wang & Wen-Sheng Xiang

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  1. Xiang-Jing Wang
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Correspondence to Wen-Sheng Xiang.

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Wang, XJ., Wang, XC. & Xiang, WS. Improvement of milbemycin-producing Streptomyces bingchenggensis by rational screening of ultraviolet- and chemically induced mutants. World J Microbiol Biotechnol 25, 1051–1056 (2009). https://doi.org/10.1007/s11274-009-9986-5

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  • DOI: https://doi.org/10.1007/s11274-009-9986-5

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