Xiao Jianping, Li Hui, Wen Shuping, Hong Wenrong
College of Biological Science and Technology, Fuzhou University.
J Gen Appl Microbiol. 2014;60(6):256-61. doi: 10.2323/jgam.60.256.
Tobramycin is an important broad spectrum aminoglycoside antibiotic widely used against severe Gram-negative bacterial infections. It is produced by base-catalyzed hydrolysis of carbamoyltobramycin (CTB) generated by S. tenebrarius. We herein report the construction of a genetically engineered S. tenebrarius for direct fermentative production of tobramycin by disruption of aprK and tobZ. A unique putative NDP-octodiose synthase gene aprK was disrupted to optimize the production of CTB, resulting in the blocking of apramycin biosynthesis and the obvious increase in CTB production of aprK disruption mutant S. tenebrarius ST316. Additional mutation on the carbamoyltransferase gene tobZ in S. tenebrarius ST316 generated a strain ST318 that produces tobramycin as a single metabolite. ST318 could be used for industrial fermentative production of tobramycin.
妥布霉素是一种重要的广谱氨基糖苷类抗生素，广泛用于治疗严重的革兰氏阴性菌感染。它是由黑暗链霉菌产生的氨甲酰妥布霉素（CTB）经碱催化水解生成的。我们在此报告了通过破坏aprK和tobZ构建用于直接发酵生产妥布霉素的基因工程黑暗链霉菌。破坏一个独特的推定NDP-辛二糖合酶基因aprK以优化CTB的生产，导致阿泊拉霉素生物合成受阻，且aprK破坏突变体黑暗链霉菌ST316的CTB产量明显增加。对黑暗链霉菌ST316中的氨甲酰转移酶基因tobZ进行进一步突变，产生了一个菌株ST318，该菌株以妥布霉素作为单一代谢产物进行生产。ST318可用于工业发酵生产妥布霉素。
