Fed-batch bioproduction of spectinomycin

Actinomycetes produce about 67% of the known antibiotics covering a wide range of chemical structures. However, their filamentous growth present several problems during industrial processes. Among these problems oxygen transfer limitation is critical. In this chapter we present the role of oxygen in spectinomycin production by a Streptomyces species. Spectinomycin, a broad spectrum antibiotic effective against penicillin resistant gonorrhea, is an aminoglycoside constituted from two glucose moieties. Its bioproduction is strongly influenced by glucose and oxygen. We have shown that for a fixed dissolved oxygen concentration, there are two specific glucose concentrations which give maximum final titers of spectinomycin. The bi-modal maximum indicates the influence of two intermediate metabolites in spectinomycin biosynthesis. We propose a mechanism for spectinomycin biosynthesis and subsequently develop a model based on this mechanism. The proposed mechanism for spectinomycin biosynthesis is validated by successfully reconstructing the air flow rate profiles. A nonlinear systems theory technique termed External Differential Representation, is implemented to reconstruct the spectinomycin bioconversion process which then predicts the spectinomycin concentration from the air flow rate profile. This signifies that spectinomycin titers in industrial fed-batch processes can be controlled if a priori information about the air flow rate profile yielding maximum spectinomycin is available.