Macrolactone natural products include many important antibiotics used as clinical drugs. According to current stage of Chinese fermentation industry of macrolactone antibiotics, the industrial strains with the production of erythromycin and avermectin were selected to improve the productivity of the most effective fraction, erythromycin A and avermectin B1a respectively, by regulating the metabolic pathway based on the biosynthetic knowledge. Meantime, the new generation of metabolic engineering strain to produce doramectin, the more effective agricultural antibiotic developed from avermectin, was also planed to construct by engineering the avermectin biosynthetic pathway. Additionally, a shikimate-overproductive strain will be developed, the fermentation and extraction process optimization also included, which will benefit the industrial production of shikimate.

The goals of this project are: i) to decrease the ratio of useless fractions, erythromycin B and C, and increase the ratio and the productivity of effective fraction, erythromycin A; ii) to improve the productivity and ratio of the most active fraction, avermectin B1a, and reduce the productivity of other avermectin fractions; iii) to construct the doramectin metabolic engineering strain and shikimate-overproductive genetic engineering strain.