Downstream Process Synthesis for Microbial Steroids.

Systematic and holistic process development, considering upstream and downstream processing simultaneously, is crucial for designing effective and economical production processes. Based on a multiphasic fermentation process, where oil is added to improve substrate solubility, a systematic approach for the purification of microbial steroids is presented. The design methodology incorporates expert knowledge in the form of heuristics to generate different downstream processing alternatives for processing the complex, multiphasic fermentation broth, and recovering the target steroid precursor androst-4-ene-3,17-dione (androstenedione; AD). The resulting alternative tree of different purification techniques is evaluated using scouting experiments to check the performance of each technique. Purification steps such as extraction, adsorption-desorption, and precipitation seem most promising and have been investigated in detail. Each process step selected is optimized and connected to a process route for recovering AD.