Arginine regulation of gramicidin S biosynthesis

Several amino acids are known to affect the gramicidin S producer Bacillus brevis ATCC 9999 with respect ot growth, soluble gramicidin S synthetase formation, antibiotic production, or a combination of these. Our studies confirmed that arginine has paradoxical effects on the B. brevis fermentation; it markedly increased growth and antibiotic production, yet decreased the soluble heavy gramicidin S synthetase activity. We found that arginine did not repress heavy gramicidin S synthetase. The amino acid stimulated growth and increased specific antibiotic production presumably by supplying a limiting precursor (ornithine) for gramicidin S synthesis. Although the amino acid decreased the specific activity of the soluble heavy gramicidin S synthetase, it markedly increased the particulate enzyme activity which persisted hours after the soluble heavy gramicidin S synthetase disappeared. One percent arginine was the optimum level for growth and gramicidin S production. After growth in 1% arginine, heavy synthetase activity in the particulate fraction more than doubled. We propose that arginine leads to the soluble enzyme becoming membrane bound and more stable in vivo. Although we found arginine capable of inhibiting the action of soluble heavy gramicidin S synthetase, this was not the mechanism involved in the lowering of soluble heavy gramicidin S synthetase specific activity.