Conceptual Process Design of Integrated Fermentation, Deacylation, and Crystallization in the Production of β-Lactam Antibiotics

Integration of fermentation and downstream steps is required to improve the sustainability of industrial biotechnology processes. In this context, a new integrated process for beta-lactam nuclei production is proposed, which has been theoretically investigated and conceptually designed. This process is an integration of fermentation and enzymatic deacylation of adipyl-7-aminodeacetoxycephalosporanic acid (adADCA) in one reactor producing 7-aminodeacetoxycephalosporanic acid (ADCA) directly from glucose. Although the deacylation equilibrium is unfavorable at the fermentation pH, it is pulled to completion because ADCA starts to crystallize and the liberated side chain, adipic acid (AA), is consumed by the fermentation. Therefore the integrated process requires much less AA than the nonintegrated process. In addition, the new process will lead to a reduction in number of downstream processing units, should avoid the use of acids and bases for pH shifts, and might lead to a reduction in waste salts production. A conceptual process was designed including an economic and technical analysis. The design goal was to produce 2000 tons/year of ADCA of 99% purity. Rigorous simulations were performed to evaluate different process options. Among the economic advantages of the new integrated process are 13.4% lower capital investments and 7.8% lower manufacturing costs. An analogous process for 6-aminopenicillanic acid (APA) is not feasible due to chemical degradation of this product.