Optimization of tylosin feeding rate profile in production of acetyl-isovaleryl tylosin (AIV) from tylosin by Streptomyces thermotolerans YN554

An optimal feed rate profile of a substrate (tylosin) for a novel antibioti c, acetyl-isovaleryl tylosin (AIV) production process was investigated. In the first step of optimization, a kinetic model for production of AIV from tylosin by Streptomyces thermotolerans was established properly using the l east square method, followed by the confirmation that the proposed model co uld be used to predict the production process of AIV from tylosin. An objec tive function, state equations and an inequality constraint with respect to the tylosin feeding rate profile were applied to maximize the amount of AI V produced from tylosin in a fed-batch culture. The optimized tylosin feedi ng rate profile was determined using a direct iterative search algorithm ba sed on the modified complex method. The simulation of AIV production at the optimal tylosin feeding profile indicates that the final amount of AIV is expected to be about 30% higher than that at the conventional constant tylo sin feeding rate, which was also confirmed experimentally using a 30-l jar fermentor.