Effects of precursors on kitasamycin production in Streptomyces kitasatoensis

Abstract

To improve kitasamycin biosynthesis by Streptomyces kitasatoensis Z-7, the addition of two precursors, sodium acetate and ethyl acetate, to the fermentation medium was evaluated. Ethyl acetate was the most effective precursor compared with control conditions; In a 15-L fermentor, the kitasamycin titer was 21% higher when 0.48% ethyl acetate was added compared to control conditions. Content of the A₅ component increased by 5.1%, and the A₄ content decreased slightly compared to that of the control. During kitasamycin synthesis, intracellular and extracellular concentrations of acetic acid were higher for S. kitasatoensis Z-7 supplemented with ethyl acetate than for the non-supplemented strain, and the activities of acyl-CoA synthetases, acyl-phosphotransferases, and acyl-kinases were also significantly increased, suggesting that increased acetyl-CoA levels can explain the high kitasamycin titer. These findings may improve the industrial-scale production of kitasamycin for clinical use, and the addition of 0.48% ethyl acetate as precursors in the medium at the beginning of cultivation was a new method to mitigate the negative influence on the cell growth of excess precursor.