Effects on productivity of avermectin by knockout of 10 polyketide biosynthetic gene clusters in Streptomyces avermitilis genome

Abstract:

[Objective] We studied whether avermectin productivity could be affected by other polyketide biosynthetic gene clusters in Streptomyces avermitilis genome. [Methods] By constructing gene knock-out cosmids or plasmids and introducing into industrial host, 10 mutants were obtained after screening double crossover colonies from conjugants of each polyketide gene clusters knocked-out vectors. [Results] Avermectin productivities of seven polyketide null mutants were higher than that of the starting strain. Two mutants abolished avermectin production. Three mutants with combined knock-out of two of three strong effect clusters had no further increase on avermectin productivity. [Conclusion] Deletions of some polyketide gene clusters can be used to increase avermectin productivities in Streptomyces avermitilis. The results also suggested that there were interweaved networks among these polyketide gene clusters in Streptomyces avermitilis.