Liu Ling, Chen Zhen, Tian Xiwei, Chu Ju
Qingdao Innovation Institute of East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, People's Republic of China.
Bioresour Bioprocess. 2025 Jan 4;12(1):1. doi: 10.1186/s40643-024-00831-y.
Cephalosporin C (CPC) is a critical raw material for cephalosporin antibiotics produced by Acremonium chrysogenum. During fermentation, the oxygen supply is a crucial factor limiting the efficient biosynthesis of CPC. This study demonstrated that the addition of exogenous surfactants significantly increased the dissolved oxygen (DO) level, extracellular catalase content, and final CPC titer. Consequently, we hypothesized and examined a correlation between catalase and CPC biosynthesis in A. chrysogenum through both the exogenous addition of hydrogen peroxide (H₂O₂) and the endogenous modulation of the catA expression level. The results indicated that both the addition of H₂O₂ and the ∆catA mutation exhibited similar fermentation trends, leading to decreased extracellular catalase activity and increased intracellular reactive oxygen species (ROS) content, which resulted in reduced CPC production. Conversely, strains that overexpress varying levels of the catA accelerated hyphal differentiation under DO-limiting conditions, reducing intracellular ROS accumulation and decreasing cellular apoptosis, which stabilized CPC yield during the later stages of fermentation. This study provides a critical foundation for further investigations into the regulatory mechanisms governing CPC biosynthesis in A. chrysogenum.
头孢菌素C（CPC）是产黄顶孢霉生产头孢菌素抗生素的关键原料。在发酵过程中，氧气供应是限制CPC高效生物合成的关键因素。本研究表明，添加外源表面活性剂可显著提高溶解氧（DO）水平、胞外过氧化氢酶含量和最终CPC效价。因此，我们通过外源添加过氧化氢（H₂O₂）和内源性调节catA表达水平，对产黄顶孢霉中过氧化氢酶与CPC生物合成之间的相关性进行了假设和研究。结果表明，添加H₂O₂和∆catA突变均呈现相似的发酵趋势，导致胞外过氧化氢酶活性降低和细胞内活性氧（ROS）含量增加，从而使CPC产量降低。相反，在DO限制条件下，过表达不同水平catA的菌株加速了菌丝分化，减少了细胞内ROS积累并降低了细胞凋亡，从而在发酵后期稳定了CPC产量。本研究为进一步研究产黄顶孢霉中CPC生物合成的调控机制提供了关键基础。
