Nutritional requirements for chloramphenicol biosynthesis in Streptomyces venezuelae

Cultures grown in a glycerol serine lactate medium were used to establish the inoculation procedure, aeration level, and trace-mineral nutrition optimizing chloramphenicol production in Streptomyces venezuelae. The stimulatory effect of lactate in this medium was concluded not to be an artifact of medium preparation but to reside in its influence on carbon-source utilization. In media with ammonium sulfate as a nonrestricting source of nitrogen, chloramphenicol production varied with the carbon source chosen. Production occurred during the growth phase and was highest on galactose, lactose, cellobiose, and starch. The rate of synthesis was related directed to the growth rate and decreased in the stationary phase. Variation of the nitrogen source with glucose as a nonrestricting source of carbon showed that the highest antibiotic titres were obtained with poorly utilized compounds such as isoleucine or phenylalanine. Proline gave yields comparable with those obtained in the more complex glycerol serine lactate medium in a shorter time. Although rate of growth is not the sole determining parameter, chloramphenicol synthesis is concluded to be a "growth-linked" process.