Replacing The Loading Module In Avermectin Biosynthesis

Avermectins is a kind of widely used biological pesticides with high efficiencyand low toxicity. It is one of the most effective insecticides, miticides and parasiticagents. It has a significant role for controlling parasites and harmful insects.Polyketides are natural products produced by various organisms such as bacteria,fungi, or plants. Polyketides are among the most important microbial metabolites inhuman medicine, because they exhibit the largest diversity in chemical structures andbiological activities. By elucidatied avermectin biosynthetic pathway and obtainedbiosynthesis gene cluster, we can alter avermectins producing strain to produce aseries of new useful natural products through metabolic engineering based on thewhole-genome sequencing information of this strain. With the in-depth study of type Ipolyketide synthase, the operation of several polyketide synthase technologydevelopment technical can be referred for the experiments in this article.The main strategies adopted is to replace the coding phosphazomycinbiosynthetic gene cluster starting module genes encoding avermectin biosyntheticgene in starting modul of clustere for the transformation from avermectin todoramectin. For the purpose to reach the change of the specificity of the loadingmodule of the starting unit, and the feed the starting unit when cultured in the originalfermentation medium so as to achieve the purpose of generating doramectin. Wesuccessfully constructed three mutants, one of them produced a small amount ofdoramectin, however, the mutant produced a small amount of the avermectin at thesame time.The same strategy is adopted for producing new avermectin derivatives, exceptthat the replacement of the loading module gene from module generatingquartomicins and FR901464strain. We successfully constructed two mutant strains.The result indicate that there is no new avermectin derivatives in the fermentation. Sothe replacement location selected need to be further optimized.