clavulanic acid
Clavulanic Acid
Product titres usually flatten in the course of a microbial fermentation but some examples are recognized of clear loss of titre caused by product degradation (Mayer, A.F. and Deckwer, W.-D. [1996] Simultaneous production and decomposition of clavulanic acid during Streptomyces clavuligerus cultivations, Applied Microbiology and Biotechnology, vol. 45, pp. 41-46; Roubos, J.A., et al. [2002] Clavulanic acid degradation in Streptomyces clavuligerus fed-batch cultivations, Biotechnology Progress, vol. 18, pp. 451-457).
Relating product degradation to global limits to productivity is key to understanding this type of bioprocess.
Clavulanic acid is (perhaps) uniquely unstable among microbial secondary metabolites but the diversion of early precursors of tetracycline antibiotics to melanoid pigments has also been found – the major limits to product formation may literally be “hiding in plain sight” (Nakano, T. et al. [2000] Mechanism of the incidental production of a melanin-like pigment during 6-demethylchlortetracycline production in Streptomyces aureofaciens, Applied and Environmental Microbiology, vol. 66, pp. 1400-1404).”
