Effects Of Precursors On Maituolaimycin Biosynthesis And The Related Metabolic Flux Analysis

The study of metabolic flux and metabolic network of a useful antibiotic is the basis of metabolic engineering to improve strain's productivities and obtain new hybrid antibiotics through the biosynthetic pathways' modification or reconstruction. To increase its production and obtain new pharmaceuticals of similar structure, the biosynthetic pathway and its related metabolic network were studied for the first time. Also it was used for further structure identification, illustrating the structural modification after polyketide biosynthesis, separating the intermediate existed in the process of maituolaimycin fermentation, and helping to explain the conversion process of the intermediate. All contents were shown as bellow: 1. Maituolaimycin was considered to be synthesized through polyketide pathway through analyzing its structure and related characteristics. Its production was dramatically inhibited after adding the inhibitor, the specific inhibitor of a key enzyme involved in the polyketide pathway. Then precursor adding experiment was done to further identify the conclusion. The result showed that maituolaimycin production was improved with the addition of acetate, propionate and butynate. Thus we have the conclusion that maituolaimycin is synthesized through polyketide pathway. 2. Optimal adding concentration and optimal adding time experiments were done to help us find the best precursor for matiuolaimycin production. Then propionate was selected as the precursor most effective for matiuolaimycin production. The media optimization experiment was done to study the interactions between factors with propionate feeding using Response Surface Methodology. And also the relationship between biomass and maituolaimycin production was observed. 3. Then the metabolic network of Streptomyces luteogriseus was established and the metabolic pathway of propionate was researched. Using information from KEGG, possible metabolic pathway of propionate involved in Streptomyces was found. Matlab was used to construe the metabolic flux and the result showed that the metabolic flux of pentosephosphate pathway was increased after the addition of propionate.