Mutation Breeding Of Anganmycin-producing Strain And The Optimization Of Fermentation Bioprocess

Anganmycin, a new nucleoside antibiotic, showed remarkable biological activity against powdery mildews of many plants with low toxicity. A systematic investigation was carried out to improve the productivity of one anganmycin-producing strain with mutation breeding and bioprocess optimization. Also, different anganmycin determination methods, primary fermentation kinetic and scaling up of fermentation process were included.(1) The chemical method for the determination of anganmycin was developed with the aid of SAKAGUCHI reaction. The rapid determination method was built with red yeast as the test mico-organism. Further studies showed that HPLC was the best method to determinate the anganmycin precisely.(2) Mutant breeding and optimization of fermentation bioprocess. According to the suggested biosynthesis pathway of anganmycin, high producing mutants were selected with the anti-metabolism activity to improve the synthesis of anganmycin after physical and chemical mutation. One highest producer, D-62-2, was obtained which could produce 1.5g/L anganmycin, about four times higher than that of the origin strain ZD615.(3) Anganmycin fermentation in 10L and 15 liter bench-top fermentors. Three different types of batch and fed-batch fermentation were carried out in the 10 liter domestic fermentor, and further test was performed in 15 liter B.Braun fermentor. With the optimization of these fermentation bioprocess, the productivity of anganmycin was improved from 0.38g/L to 0.8g/L, which only showed 53% of the productivity in the shaking flask.(4) Kinetic study of anganmycin fermentation. According to the experimental data and the supposed model, the kinetic equations including the growth of mycelium, the consumption of substrate and the production of anganmycin were obtained with the use of Matlab software:. These equations are as(5) The anganmycin fermentation process was scaled up in a pharmaceutic factory. Six runs of experiments was performed on 250L, 700L and 2500L fermentor respectively. The highest productivity of anganmycin (0.628g/L) was achieved , and some important problem was also discussed here.