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

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 0 -nitroso-N-nitrosoguanidine (NTG) mutation was performed to obtain high milbemycin-producing S. bingchenggensis. Aminoacetic acid (Glycine)-resistant mutants (AA r ), propionate-resistant mutants (PRP r ), streptomycin-resistant mutants (STR r ) and 2-deoxy-D-glucoseresistant mutants (DOG r ) were selected successively. A strain S. bingchenggensis BC-109-6 with AA r , PRPr, STR r and DOG r was obtained and its production of milbemycin A3 and A4 reached 1,450 lg/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 lg/ml after 360 h batch fermentation.

New milbemycins from mutant Streptomyces bingchenggensis X-4

“…Proton Carbon In compound 1, the large J (14.6 Hz) of H-10 and H-11 and the NOESY crossing peaks (Figure 1) between H 2 -27 and H-10, H 3 -29 and H 2 -16 indicated that the three double bonds at C-8 and C-9, C-10 and C-11, C-14 and C-15 were E. The NOESY correlations of H-17, H 3 -30 and H-25, H-17 and H-19, H-11 and H 3 -28 suggested that these protons having the same orientations as in milbemycin b 12 .…”

“…12 The culture temperature was 28 1C and the initial pH was 7.40 sterilized by sparging with steam at 121 1C for 30 min. The dissolved oxygen was maintained above 35% by adjusting the agitation speed.…”

New 5-oxomilbemycins from a Genetically Engineered Strain Streptomyces bingchenggensis BCJ60

“…noncyanogenus and Streptomyces thermoarchaensis [16]. Apart from the mentioned strains, another newly milbemycin-producing strain Streptomyces bingchenggensis was isolated by our research team and currently used as an industrial producer of milbemycins [17]. S. bingchenggensis produces milbemycins A3/A4, two α-class milbemycins (B2/B3) and two β-class milbemycins (β 1 /β 2 ) as its major components together with the polyether ionophore nanchangmycin and a trace of new milbemycin analogs, including α 28 , α 29 , α 30 , β 13 , β 14 , ST906, and secomilbemycins A and B [18,19].…”

Obtaining of highly active streptomycin-resistant bacteriolysins’s producers of Streptomyces albus

“…Аналіз сучасних методів та прийомів в селекції мікробних продуцентів біологічно активних речовин свідчить про важливе значення гено типу вихідного штаму для отримання над продуцентів, а також про доцільність багатостадійної обробки культури послідовно різними типами мутагенів [2][3][4].…”

“…Так, використання УФ випромінювання дало змогу отримати надпродуценти родів Bacillus та Coniothyrium з підвищеним у 2-10 разів рівнем біосинтезу фермен тів [5,6], cтупінчаста обробка УФ випромінюванням та хімічними мутагенами стала ефективною в селекції продуцентів антибіотиків та ферментів родів Streptomyces, Pseudomonas та інших [3,4].…”