Enhancement of natamycin production by combining ARTP mutagenesis with temperature control strategy development in Streptomyces gilvosporeus.

Natamycin, a natural antifungal compound produced by Streptomyces, possesses antibacterial activity against yeast and mold. However, its low yield hinders widespread application in the food and pharmaceutical industries. This study aims to enhance natamycin production of Streptomyces gilvosporeus through engineering strain and optimization bioprocess. A high-yield strain exhibiting robust genetic stability was bred, yielding a 19.8% increase in shake flask fermentation and a 26.3% increase in fed-batch fermentation compared to the starting strain. The influence of temperature on high-yield strains was examined separately through batch fermentation and fed-batch fermentation. Subsequently, based on comprehensive analysis of fermentation kinetic parameters, a two-stage temperature control strategy was proposed. Specifically, the temperature was maintained at 30 ℃ for the first 18 h to shorten the lag phase, followed by a reduction to 26 ℃ and maintaining this temperature until the end of fermentation. Under this strategy, the natamycin production reached 14.4 g·L, representing a 25.2% increase compared to constant temperature fermentation at 28 ℃. This study provided an efficient production strategy for natamycin.