Improvement in natamycin production by Streptomyces natalensis with the addition of short-chain carboxylic acids

• Natamycin production enhanced by addition of short chain carboxylic acids.
• Carboxylic acid addition should be during the exponential growth phase.
• Maximal antibiotic production achieved by addition of acetate–propionate mixture.

Natamycin is an important tetraene (polyene) antibiotic produced in submerged culture by different strains of Streptomyces sp. In the present work, the effects of the addition of short-chain carboxylic acids (acetic, propionic and butyric) on cell growth and the kinetics of natamycin production were investigated during submerged cultivation of Streptomyces natalensis. The addition of acetic and propionic acids showed stimulatory effects on natamycin production when added to the fermentation medium at concentrations below 2 g L−1 at the beginning of cultivation. In addition, when acetic and propionic acids were added in a mixture (7:1) at a total concentration of 2 g L−1, antibiotic production increased significantly, reaching 3.0 g L−1 (approximately 223% and 250% increases in volumetric and specific antibiotic production, respectively, compared with the control culture). Moreover, the addition of carboxylic acids not only increased the antibiotic yield but also decreased the production time from 96 h to only 84 h in shake-flask cultures. A further enhancement in natamycin production was achieved by cultivation in a 2-L stirred-tank bioreactor under controlled pH conditions. The maximum volumetric production of 3.98 g L−1 was achieved after 84 h in carboxylic acid-supplemented culture (acetate and propionate in a ratio of 7:1).