Ansamitocin P-3 Production Using Industrial By-products As Carbon And Nitrogen Sources

Ansamitocin P-3 is highly potential antitumor maytansinoid,which is a product by Actinosynnema pretiosum spp..Due to its high cytotoxity effect,nowadays AP-3 linked drugs are undergoing clinical trials for treatment of breast,pancrealtic cancer cells.Though a lot of work was done to improve ansamitocin P-3 titer,the low titer still becomes a bottleneck for its industrialization.Usually,synthetic media for ansamitocin P-3 fermentation are used.In the present work,we focused on the development of culture medium with industrial by-products.Firstly,we have screened nitrogen sources;soybean powder seemed to be the best nitrogen source for AP-3 production,although,the high concentration was found to inhibit AP-3 production.In order to understand the inhibition by high concentration of soybean powder,two media with high and low concentration of soybean powder were investigated.Differences were assayed in gene transcription and fermentation performance between two media.Transcriptional studies revealed that the up-regulated genes were responsible for carboxylation of malonyl Co-A and encoding 2-methoxymalonyl-ACP.Secondly,cane molasses and glycerol were defined as low-cost carbon sources for AP-3 production.After that,response surface methodology(RSM)was used for statistical optimization of medium.Box-Behnken design was applied to determine mutual interaction effect of tested variables on ansamitocin P-3 titer and to find optimal concentration of tested variables.Results of Box-Behnken design suggested the optimum solution,which was as follow(g/L):cane molasses 63.23,glycerol 22.91,and soybean powder 3.29.The validation experiment with optimum solution was carried out in triplicate and AP-3 production of 111.9410.91 mg/L was obtained.To sum up,using cheap industrial by-products such as cane molasses,glycerol and soybean powder is effective and commercially feasible.