Molecular identification of the transcriptional activator of carotenoid biosynthesis in the fungus Fusarium fujikuroi

类胡萝卜素包括600多种不同的化合物，具有多种不同的特性。其中许多是细菌、植物和真菌次生代谢的关键元素。由于它们的个体能力，它们在保护个体免受光诱导或氧化损伤方面提供了很大一部分分子任务，这反映了它们对所有真核生物的重要性。动物和人类都不能产生类胡萝卜素。然而，它们是形成维生素A和保护黄斑的先决条件。据此，人类必须从饮食中摄取足量的类胡萝卜素。在发展中国家普遍存在的供应不足导致视力、皮肤成分和免疫系统的严重缺陷。真菌系统为工业生产天然类胡萝卜素提供了极好的来源，从而避免了作为化学合成典型副产物的生物无活性异构体。此外，真菌需要的条件很少，易于培养，并且由于它们的可发酵性，可以产生大量的次生代谢物。为了优化工业生产，真菌类胡萝卜素生物合成的组成和调控的详细知识是重要的。自20世纪80年代以来，植物病原菌Fusarium fujikuroi作为真菌模型系统研究类胡萝卜素的生物合成。由于对宿主的研究已经完成，所有参与类胡萝卜素合成的蛋白质的结构基因都是已知的，而这些基因的调控尚不清楚。该项目的目的是表征类胡萝卜素途径的新调节蛋白，如预测的CarC，一种尚未描述的类胡萝卜素生物合成的正调节蛋白，预计将与已经描述的负调节蛋白car相互作用。为此，针对CarC的特定特征，将利用Co免疫沉淀实验、pull-down实验和酿酒酵母的异源表达。这些实验将产生一份可信的潜在候选人名单。相应基因的遗传缺失，随后对所产生的表型进行深入分析，将作为对照实验，同时也为CarC潜在的次要作用提供详细的见解。申请人已经在蛋白质-蛋白质相互作用和真菌蛋白质复合物领域拥有强大的背景，非常有资格进行目标实验。由于宿主群是fujikuroi研究的主要设施之一，并且已经确定了类胡萝卜素生物合成所需的结构基因，因此此次合作将填补该调控研究中剩下的最后科学空白。所获得的结果可能有助于优化真菌类胡萝卜素的工业生产，进一步防止人群维生素a供应不足。

Carotenoids include over 600 different chemical compounds, bearing a large variety of different characteristics. Many of them are key elements of secondary metabolism of bacteria, plants, and fungi. Due to their individual abilities, they provide a large subset of molecular tasks in protecting individuals against light induced or oxidative damage, which reflects their importance for all classes of eukaryotic life. Animals and humans are unable to produce carotenoids. Nevertheless, they are prerequisites for the formation of Vitamin A, and for the protection of the macula lutea. According to this, humans have to incorporate a sufficient amount of carotenoids through their diets. An undersupply, which is common in developing countries, leads to severe defects in vision, skin composition, and the immune systemFungal systems provide an excellent source for the industrial production of natural carotenoids, thereby avoiding biological inactive isomers which are typical byproducts of chemical synthesis. Additionally, fungi need few requirements, are easy to cultivate and, due to their fermentability, can produce enormous amounts of secondary metabolites. To optimize the industrial production, detailed knowledge about the composition and regulation of fungal carotenoid biosynthesis is important.The plant pathogen Fusarium fujikuroi serves as a fungal model system to study carotenoid biosynthesis since the 1980´s. Due to the already performed research of the host group, the structural genes for all proteins involved in the synthesis of carotenoids are known, whereas the regulation of these genes remains unclear. The aim of this project is to characterize novel regulatory proteins of the carotenoid pathway, such as the predicted CarC, a yet undescribed positive regulator of carotenoid biosynthesis expected to interact with the already described negative regulator CarS. For this, Co Immunoprecipitation experiments, pull-down assays, and a heterologous expression in S. cerevisiae will be utilized, aiming at specific characteristics attributed to CarC. These experiments will lead to a credible list of potential candidates. Genetic deletions of the corresponding genes, followed by in depth analyses of the resulting phenotypes, will serve as control experiments and, simultaneously, provide detailed insights also into potential secondary roles of CarC.Already having a strong background in the field of protein-protein interaction and fungal protein complexes, the applicant is highly qualified to perform the targeted experiments. As the host group is one of the leading facilities in the research on F. fujikuroi and has already characterized the structural genes needed for the carotenoid biosynthesis, the collaboration will close the last scientific gap left in the investigation of the regulation. The obtained results may contribute to optimize the industrial production of carotenoids in fungi, further preventing a Vitamin A undersupply of the population.