Xue Jian, Xiao Wen, Xu Yuxiu, Wang Liang, Zhang Jianhua, Zhang Hongjian, Chen Xusheng
Key Laboratory of Industrial Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, 1800 Lihu Road, Wuxi, 214122, Jiangsu, China.
Bioprocess Biosyst Eng. 2025 May;48(5):817-827. doi: 10.1007/s00449-025-03145-1. Epub 2025 Mar 18.
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.
纳他霉素是一种由链霉菌产生的天然抗真菌化合物，对酵母和霉菌具有抗菌活性。然而，其低产量阻碍了它在食品和制药行业的广泛应用。本研究旨在通过工程菌株和优化生物工艺来提高吉尔伏链霉菌的纳他霉素产量。培育出了一株具有强大遗传稳定性的高产菌株，与出发菌株相比，摇瓶发酵产量提高了19.8%，补料分批发酵产量提高了26.3%。通过分批发酵和补料分批发酵分别考察了温度对高产菌株的影响。随后，在对发酵动力学参数进行综合分析的基础上，提出了两阶段温度控制策略。具体而言，在发酵的前18小时将温度维持在30℃以缩短延迟期，随后将温度降至26℃并维持该温度直至发酵结束。在此策略下，纳他霉素产量达到14.4 g·L，与28℃恒温发酵相比提高了25.2%。本研究为纳他霉素提供了一种高效的生产策略。
