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 S. 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.