Light-dependent coordination of development and secondary metabolism in the filamentous fungus Aspergillus nidulans

丝状真菌构巢曲霉的无性繁殖被光加速，而在封闭的保护越冬子实体内的有性孢子优先在黑暗中形成。分化程序与不同的次级代谢途径密切相关，这些途径由基因编码，这些基因在真菌中通常聚集在一个染色体位点上。次级代谢物生物合成基因簇在营养生长期间沉默，并且仅在特定条件下例如在发育期间表达。该研究项目旨在表征同源/异源二聚体转录调节因子，表观遗传甲基转移酶和底物受体之间的相互作用，用于蛋白质降解和真菌发育，毒力和次级代谢。重点介绍了它们在发育和次生代谢产物形成中的作用。nidulans和A.烟熏。将分析彼此相互作用以及与不同Vap-Vip甲基转移酶相互作用的天鹅绒结构域蛋白，以及E3 cullin RING泛素连接酶的F-box蛋白底物受体。150-200个氨基酸的天鹅绒结构域为数百个真菌基因提供DNA结合和二聚化，以协调发育和次级代谢。异源二聚体的形成可以通过亚基的合成和降解或通过翻译后修饰的受控添加和去除来控制。只有天鹅绒蛋白VelB被插入的内在无序结构域（IDD）中断，可以是两个不同的异二聚体的一部分：VosA-VelB延迟无性发育，促进孢子活力，而VeA-VelB支持性发育。我们将探讨是否插入VelB固有无序结构域（IDD）提供选择性异源二聚体形成（VosA）作为额外的控制水平，这可能与其他控制机制相结合的稳定性，翻译后修饰或位置。助理nidulans VapB-VipC系统与A.烟曲霉，其携带天鹅绒相互作用蛋白VipC（VipC 1，VipC 2）的两个同源基因，并且包括具有或不具有VapB的菌株，并且其中将探索对致病性的影响。细胞蛋白质稳定性控制和遗传网络之间的联系，光控制真菌的发展，次生代谢和毒力将通过真菌F-box蛋白受体亚基，识别引发底物的特征进行检查泛素化。74个推测的F-box蛋白底物受体基因。构巢蛋白包括七种发育特异性受体。我们在过去几年中构建的Fbox蛋白编码基因的缺失集合将允许研究天鹅绒结构域蛋白的降解，以及Fbx在次级代谢、应激反应、发育和（至少对于Fbx 15）毒力中的功能。

Asexual reproduction of the filamentous fungus Aspergillus nidulans is accelerated by light, whereas sexual spores within closed protecting overwintering fruiting bodies are preferentially formed in darkness. Differentiation programs are tightly connected to distinct secondary metabolic pathways, which are encoded by genes, which are in fungi often clustered on one chromosomal locus. Secondary metabolite biosynthetic gene clusters are silenced during vegetative growth and only expressed under specific conditions as e.g. during development. This research project aims to characterize the interplay between homo/hetero-dimeric transcriptional regulators, epigenetic methyltransferases and substrate receptors for protein degradation and fungal development, virulence and secondary metabolism. The focus is on their functions in development and secondary metabolite formation in A. nidulans and virulence in A. fumigatus. Velvet domain proteins interacting with each other and with different Vap-Vip methyltransferases, and F-box protein substrate receptors of E3 cullin RING ubiquitin ligases will be analyzed. The 150-200 amino acid velvet domain provides DNA binding and dimerization to hundreds of fungal genes to coordinate development and secondary metabolism. Heterodimer formation can be controlled by the synthesis and degradation of subunits or by controlled addition and removal of posttranslational modifications. Only the velvet protein VelB is interrupted by an insertion of an intrinsically disordered domain (IDD) and can be part of two different heterodimers: VosA-VelB delays asexual development and promotes spore viability, whereas VeA-VelB supports sexual development. We will explore whether the inserted VelB intrinsically disordered domain (IDD) provides selective heterodimer formation (for VosA) as additional level of control, which might be combined with other control mechanisms as stability, posttranslational modifications or location. The A. nidulans VapB-VipC system will be compared with A. fumigatus, which carries two isogenes for velvet interacting protein VipC (VipC1, VipC2) and includes strains with or without VapB and where the impact on pathogenicity will be explored. The link between cellular protein stability control and genetic networks for light-controlled fungal development, secondary metabolism and virulence will be examined through the characterization of fungal F-box protein receptor subunits, which recognize primed substrates to be ubiquitinated. The 74 genes for putative F-box protein substrate receptors of A. nidulans include seven developmental-specific receptors. The deletion collection of Fbox protein encoding genes, which we have constructed during the last years, will allow to study degradation of velvet domain proteins, but also the function of Fbx in secondary metabolism, stress response, development and (at least for Fbx15) virulence.