菌丝形态发育：丝状真菌细胞工厂遗传改造的新切入点

Filamentous morphology: a new frontier for genetic modification of filamentous fungal cell factories

摘要:

丝状真菌是一类广泛存在于自然界中的真核微生物，一些丝状真菌因具有强大的蛋白分泌能力或者可以有效合成许多活性物质被开发为“细胞工厂”，常被用于酶制剂、重组蛋白、有机酸以及次级代谢产物的生产。丝状真菌菌体的生长形态对工业发酵具有关键意义，对发酵产品的品质及发酵过程的控制均有显著影响。本课题组前期研究发现丝状真菌的菌丝形态直接影响着菌体的蛋白分泌，菌丝分枝的增多会使液体发酵时蛋白质的分泌量增加。随着丝状真菌形态研究的深入，对改变真菌菌丝体形态以提高发酵过程中目标代谢物产量的研究日益增多。尽管在真菌发酵形态与生产力的关系方向已有少量综述，但该领域的研究发展非常迅速，亟待更新。本文在对国内外相关研究报告进行大量调研的基础上，结合作者科研团队自己的研究发现，系统综述了丝状真菌的形态特征、真菌形态对工业发酵的影响及菌丝形态调控的方法和策略，以期增强国内相关学者对丝状真菌菌丝形态发育的认识，为合理开发适用于工业发酵的工程菌株提供思路。

Abstract:

Filamentous fungi are a group of eukaryotic microorganisms widely found in nature. Some filamentous fungi have been developed as “cell factories” and extensively used for the production of recombinant proteins, organic acids, and secondary metabolites due to their strong protein secretion capabilities or effective synthesis of many natural products. The growth morphology of filamentous fungi significantly influences the quality and quantity of fermented products. Previous research conducted by the authors’ group revealed that an increase in hyphal branches leads to enhanced protein secretion during liquid fermentation. With the development of morphological engineering of filamentous fungi, an increasing number of studies have focused on modifying fungal mycelium morphology to improve the yield of target metabolites during fermentation. While there have been a few reviews on the relationship between fungal fermentation morphology and productivity, research in this area is rapidly developing and requires updates. The paper presents a comprehensive review of domestic and international research reports, along with the authors’ own research findings, to systematically review the morphological patterns of filamentous fungi, the impact of fungal morphology on industrial fermentation, as well as methods and strategies for regulating mycelial morphology. The aim of this review is to enhance the understanding of relevant domestic scholars regarding the morphological development of filamentous fungi and provide ideas for the rational engineering of fungal strains suitable for industrial fermentation.