Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin, 300350, PR China; Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Yaguan Road 135, Jinnan District, Tianjin, 300350, PR China.
Tianjin Key Laboratory of Animal and Plant Resistance, College of Life Science, Tianjin Normal University, Binshuixi Road 393, Xiqing District, Tianjin 300387, PR China.
Bioresour Technol. 2023 Sep;383:129229. doi: 10.1016/j.biortech.2023.129229. Epub 2023 May 25.
Fengycin possesses antifungal activity but has limited application due to its low yields. Amino acid precursors play a crucial role in fengycin synthesis. Herein, the overexpression of alanine, isoleucine, and threonine transporter-related genes in Bacillus subtilis increased fengycin production by 34.06%, 46.66%, and 7.83%, respectively. Particularly, fengycin production in B. subtilis reached 871.86 mg/L with the addition of 8.0 g/L exogenous proline after enhancing the expression of the proline transport-related gene opuE. To overcome the metabolic burden caused by excessive enhancement of gene expression for supplying precursors, B. subtilis and Corynebacterium glutamicum which produced proline, were co-cultured, which further improved fengycin production. Fengycin production in the co-culture of B. subtilis and C. glutamicum in shake flasks reached 1554.74 mg/L after optimizing the inoculation time and ratio. The fengycin level in the fed-batch co-culture was 2309.96 mg/L in a 5.0-L bioreactor. These findings provide a new strategy for improving fengycin production.
丰原素具有抗真菌活性，但由于产量低，其应用受到限制。氨基酸前体在丰原素合成中起着至关重要的作用。本文通过在枯草芽孢杆菌中过表达丙氨酸、异亮氨酸和苏氨酸转运相关基因，使丰原素的产量分别提高了 34.06%、46.66%和 7.83%。特别是，在增强脯氨酸转运相关基因 opuE 的表达后，添加 8.0 g/L 外源脯氨酸，使丰原素的产量达到 871.86 mg/L。为了克服因过量表达基因以提供前体而导致的代谢负担，枯草芽孢杆菌和产脯氨酸的谷氨酸棒杆菌被共培养，这进一步提高了丰原素的产量。在优化了接种时间和比例后，摇瓶中枯草芽孢杆菌和谷氨酸棒杆菌共培养的丰原素产量达到 1554.74 mg/L。在 5.0-L 生物反应器中，补料分批共培养的丰原素水平达到 2309.96 mg/L。这些发现为提高丰原素的产量提供了一种新的策略。
