Unexpected enhancement of beta-lactam antibiotic formation in Streptomyces clavuligerus by very high concentrations of exogenous lysine.

L-Lysine is known to stimulate production of beta-lactam antibiotics by Streptomyces clavuligerus via provision of the lysine breakdown product, L-alpha-aminoadipic acid, which is a limiting precursor. Previous investigations utilized levels of 10-20 mM L-lysine as an addition to chemically-defined media resulting in 50-100% improvement in antibiotic production. We were surprised to note that as the concentration was further increased, the organism responded by producing even higher titers of antibiotics. The optimum concentration of 100 mM L-lysine yielded an approximate 500% increase in production with only minor effects on growth. DL- and D-Lysine also exerted enhancements suggesting the presence of a lysine racemase or some other route from D-lysine to L-alpha-aminoadipate in this organism; D-lysine was considerably less potent than DL- or L-lysine.