Effect of water activity on production of β-lactam antibiotics by Streptomyces clavuligerus in submerged culture

The amount of available water in the environment of micro-organisms, defined as water activity (a(w)), has been shown to affect growth, respiration, enzyme synthesis, sporulation and other physiological functions. The aim of this study was to examine the impact of a(w) on production/excretion of a secondary metabolite. For this purpose, the production of β-lactam antibiotics and biomass of Streptomyces clavuligerus was studied in relation to the a(w)-depressing agents glucose, sorbitol and NaCl. These were chosen because NaCl and sorbitol are often used to depress a(w) and glucose was not thought to be taken up by 5. clavuligerus. The filamentous bacterium S. clavuligerus NRRL 3585 (ATCC 27064) is a prokaryotic producer of penicillin N, cephalosporins including cephamycin C and clavulanic acid. Under water stress conditions, a greater effect upon antibiotic biosynthesis than upon growth was consistently observed. When a(w) was decreased to below 0.997, antibiotic production began to decrease. For growth, inhibition was much more gradual and did not become intensive until an a(w) of 0.990 was reached.