Zhang Kai, Zhao Shanshan, Wang Zhengran, Cheng Ming, Wang Wan, Yang Qian
Donghai Laboratory, Zhoushan 316021, China.
School of Life Science, Ludong University, 186 Hongqi Road, Yantai 264025, China.
Foods. 2025 Feb 28;14(5):842. doi: 10.3390/foods14050842.
Chaetoglobosin A (CheA), a typical structure of the cytochalasin family, exhibits outstanding efficacy against a variety of tumor cells and plant pathogens. However, its low yield and high production cost are major obstacles limiting its wide application. In order to increase CheA yield, an engineered strain was established by overexpressing , the gene encoding the MFS family's efflux pump, on chassis cells lacking , which have been shown to act as a negative regulator of CheA biosynthesis. As expected, the engineered strain significantly boosted CheA production from 63.19 to 265.93 mg/L after incubation in PDA medium for 10 d, whereas the yield of the engineered strain was remarkably enhanced 2.93-fold compared with the wild type, following 10 d of cultivation utilizing potato starch industrial waste. The addition of metal ions had a positive effect on CheA production, with Cu being the most effective and improving production to 176.92 mg/L. The optimal fermentation conditions were determined by response surface optimization, and under the optimal conditions, the engineered strain could stably produce CheA with a yield of 197.58 mg/L. This study provided the conditions for reducing production costs while increasing CheA production, as well as new strategies and insights for the production of the target compound.
球毛壳菌素A（CheA）是细胞松弛素家族的典型结构，对多种肿瘤细胞和植物病原体具有显著疗效。然而，其低产量和高生产成本是限制其广泛应用的主要障碍。为了提高CheA产量，通过在缺乏已被证明是CheA生物合成负调控因子的底盘细胞上过表达编码MFS家族外排泵的基因，构建了一种工程菌株。不出所料，该工程菌株在PDA培养基中培养10天后，CheA产量从63.19毫克/升显著提高到265.93毫克/升，而在利用马铃薯淀粉工业废料培养10天后，该工程菌株的产量比野生型显著提高了2.93倍。金属离子的添加对CheA产量有积极影响，其中铜最为有效，可将产量提高到176.92毫克/升。通过响应面优化确定了最佳发酵条件，在最佳条件下，该工程菌株能够稳定地生产CheA，产量为197.58毫克/升。本研究为降低生产成本同时提高CheA产量提供了条件，也为目标化合物的生产提供了新的策略和见解。
