Abstract：
Fungi, as an important industrial microorganism, play an essential role in the production of natural products (NPs) due to their advantages of utilizing cheap raw materials as substrates and strong protein secretion ability. Although many metabolic engineering strategies have been adopted to enhance the biosynthetic pathway of NPs in fungi, the fungal cell wall as a natural barrier tissue is the final and key step that affects the efficiency of NPs synthesis. To date, many important progresses have been achieved in improving the synthesis of NPs by regulating the cell wall structure of fungi. In this review, we systematically summarize and discuss various strategies for modifying the cell wall structure of fungi to improve the synthesis of NPs. At first, the cell wall structure of different types of fungi is systematically described. Then, strategies to disrupt cell wall integrity (CWI) by regulating the synthesis of cell wall polysaccharides and binding proteins are summarized, which have been applied to improve the synthesis of NPs. In addition, we also summarize the studies on the regulation of CWI-related signaling pathway and the addition of exogenous components for regulating CWI to improve the synthesis of NPs. Finally, we propose the current challenges and essential strategies to usher in an era of more extensive manipulation of fungal CWI to improve the production of fungal NPs.
摘要：
真菌,作为一种重要的工业微生物,由于其利用廉价原料作为底物和强大的蛋白质分泌能力的优势，在天然产物（NPs）的生产中起着至关重要的作用。尽管已经采用了许多代谢工程策略来增强真菌中NPs的生物合成途径，真菌细胞壁作为天然屏障组织是影响NPs合成效率的最后和关键步骤。迄今为止,在通过调控真菌细胞壁结构提高NPs合成方面取得了许多重要进展。在这次审查中,我们系统地总结和讨论了修改真菌细胞壁结构以改善NPs合成的各种策略。起初,系统地描述了不同类型真菌的细胞壁结构。然后，总结了通过调节细胞壁多糖和结合蛋白的合成来破坏细胞壁完整性（CWI）的策略，已应用于改进NP的合成。此外,我们还总结了CWI相关信号通路的调控以及添加外源成分调控CWI以改善NPs合成的研究。最后,我们提出了当前的挑战和必要的策略，以迎来更广泛的真菌CWI操作的时代，以提高真菌NPs的生产。
