Genome Shuffling Mutant of Streptomyces diastatochromogenes for Substantial Improvement of Toyocamycin Production
Genome Shuffling Mutant of Streptomyces diastatochromogenes for Substantial Improvement of Toyocamycin Production
复制标题
产色链霉菌基因组改组突变体显着提高丰加霉素产量
DOI：
10.3390/fermentation8100535
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发表时间：
2022-10-01
影响因子：
3.7
通讯作者：
Shentu，Xuping
中科院分区：
文献类型：
--
作者：
Song，Yang;Zhang，Zixuan;Shentu，Xuping
丰霉素是一种核苷类抗生素，是一种具有控制植物病原体潜力的杀菌剂。本研究通过三轮基因组改组筛选来提高裂殖变色链霉菌1628的托霉素产量。经过三轮基因组重组筛选，该菌株的产生量比野生型提高了10.8倍，比亲本菌株提高了2.64倍。通过对其发酵条件的优化，在产TY的发酵条件下，最高产量可达1173.6 mg/L。此外，还对混洗菌株的改良机理进行了探讨。玩具霉素产量增加的重组子表现出更高的玩具簇转录水平和产品抗性。此外，ATP水解率的上升表明，细胞内的ATP通过与ATP结合的途径特异性调节因子在调节玩具簇方面发挥了重要作用。综上所述，本研究获得了产生菌素含量较高的裂殖酵母致变色基因突变体，为次生代谢物的活化提供了有价值的线索。
Toyocamycin, a nucleoside antibiotic, is a fungicide with the potential to control plant pathogens. In this study, three rounds of genome shuffling screening were applied to enhance the toyocamycin production in Streptomyces diastatochromogenes 1628. After three rounds of genome-shuffling screening, the toyocamycin production increased by 10.8-fold that of wild-type, and 2.64-fold of its parental strain. By optimization of its nutrition condition in medium, the highest production of toyocamycin reached 1173.6 mg/L in TY-producing medium. In addition, the mechanism for the improvement of shuffled strains was investigated. Recombinants with increased toyocamycin production exhibited higher transcriptional level of the toy cluster and product resistance. Furthermore, the rise of ATP hydrolysis rate indicated that intracellular ATP exhibit a significant role in tuning the toy cluster by an ATP-binding pathway-specific regulator. In all, we obtained S. diastatochromogenes mutants with enhanced toyocamycin production, and provided a valuable clue for the activation of secondary metabolites.