Investigating the Molecular Crosstalk of Cellulose and Hemicellulose Perception in Filamentous Fungi

由于它们在生物质矿化中的作用，真菌在全球碳循环中是不可或缺的。此外，丝状真菌作为生物炼制酶的来源具有重要的经济意义。真菌生产的植物细胞壁降解酶与生物量的组成密切相关。其基础是分子信号级联导致从多糖中释放糖的感知。然而，对我们来说，信号通路在很大程度上仍然是一个黑盒子，阻碍了通过合理设计来改善酶、纤维素燃料和化学生产的工业菌株。对真菌如何感知和整合来自底物的信号，并微调其分泌的酶以准确地适应手头的生物质组成的理解，将极大地受益于生物炼制的生物质分解。在我们试图阐明丝状子囊菌粗神经孢子虫的植物细胞壁感知过程中，我们已经获得了证据，证明并非所有的糖都是独立感知的，但有些途径重叠，从而可能发生相互抑制，就像纤维素和甘露聚糖信号传导一样。此外，我们发现这种串音在工业相关物种里氏木霉和嗜热丝霉菌中也被保守。由于甘露聚糖存在于大多数木质纤维素生物质中，并且很难通过化学（预处理）处理从纤维素和其他半纤维素中选择性地去除，因此必须通过其他方法处理串扰。解决这个问题的一个很有希望的方法可能是对真菌生产宿主的信号通路进行基因工程。因此，在当前的应用中，我们提出了一个研究计划，以阐明这种串扰在N. crassa， T. reesei和M. thermophila中的潜在机制，目的是通过基因工程解除这种潜在的抑制，从而实现无限制的纤维素酶生产。此外，阐明控制这些事件的分子机制也将有力地加强未来生物炼制工业真菌菌株工程的努力。

Due to their role in biomass mineralization, fungi are indispensable for the global carbon cycle. In addition, filamentous fungi are of great economic importance as source of enzymes for the biorefinery. The production of plant cell wall degrading enzymes by fungi is finely tuned to the composition of the biomass. The basis for this are molecular signaling cascades leading to the perception of sugars liberated from the polysaccharides. However, the signaling pathways are still largely a black box to us, hampering the industrial strain improvement for enzyme, cellulosic fuel and chemical production by rational design. Biomass decomposition for biorefinery will highly benefit from an increased understanding of how fungi perceive and integrate the signals coming from the substrate and fine-tune their secreted enzymes to exactly fit the composition of the biomass at hand. In our attempts to elucidate plant cell wall perception in the filamentous Ascomycete Neurospora crassa, we have obtained evidence that not all sugars are perceived independently, but that some pathways overlap such that a reciprocal inhibition can occur, as is the case for cellulose and mannan signaling. Moreover, we found this crosstalk to be conserved in the industrially relevant species Trichoderma reesei and Myceliophthora thermophila. Since mannans are present in most lignocellulosic biomass and are very difficult to be selectively removed from cellulose and other hemicelluloses by chemical (pre-)treatments, the crosstalk has to be dealt with by other methods. A promising solution to this problem might be genetic engineering of the signaling pathways in the fungal production hosts. In the current application, we therefore propose a research program to elucidate the underlying mechanisms of this crosstalk in N. crassa, T. reesei and M. thermophila with the goal to relief them from this potential inhibition by genetic engineering and achieve unrestrained cellulase production. Moreover, the elucidation of the molecular mechanisms controlling these events will also strongly fasten future industrial fungal strain engineering efforts for the biorefinery.