Becker Kordula, Beer Christina, Freitag Michael, Kück Ulrich
Christian Doppler Laboratory for Fungal Biotechnology, Lehrstuhl für Allgemeine und Molekulare Botanik, Ruhr-Universität Bochum, Universitätsstr. 150, D-44780, Bochum, Germany.
Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon, 97331-7305, USA.
Mol Microbiol. 2015 Jun;96(5):1002-22. doi: 10.1111/mmi.12987. Epub 2015 Mar 28.
Penicillium chrysogenum is the main industrial producer of the β-lactam antibiotic penicillin, the most commonly used drug in the treatment of bacterial infections. Recently, a functional MAT1-1 locus encoding the α-box transcription factor MAT1-1-1 was discovered to control sexual development in P. chrysogenum. As only little was known from any organism about the regulatory functions mediated by MAT1-1-1, we applied chromatin immunoprecipitation combined with next-generation sequencing (ChIP-seq) to gain new insights into the factors that influence MAT1-1-1 functions on a molecular level and its role in genome-wide transcriptional regulatory networks. Most importantly, our data provide evidence for mating-type transcription factor functions that reach far beyond their previously understood role in sexual development. These new roles include regulation of hyphal morphology, asexual development, as well as amino acid, iron, and secondary metabolism. Furthermore, in vitro DNA-protein binding studies and downstream analysis in yeast and P. chrysogenum enabled the identification of a MAT1-1-1 DNA-binding motif, which is highly conserved among euascomycetes. Our studies pave the way to a more general understanding of these master switches for development and metabolism in all fungi, and open up new options for optimization of fungal high production strains.
产黄青霉是β-内酰胺抗生素青霉素的主要工业生产菌，青霉素是治疗细菌感染最常用的药物。最近，发现一个编码α-box转录因子MAT1-1-1的功能性MAT1-1基因座可控制产黄青霉的有性发育。由于对于任何生物体中由MAT1-1-1介导的调控功能知之甚少，我们应用染色质免疫沉淀结合新一代测序（ChIP-seq）技术，以在分子水平上深入了解影响MAT1-1-1功能的因素及其在全基因组转录调控网络中的作用。最重要的是，我们的数据为交配型转录因子的功能提供了证据，这些功能远远超出了其先前在有性发育中所理解的作用。这些新作用包括对菌丝形态、无性发育以及氨基酸、铁和次级代谢的调控。此外，体外DNA-蛋白质结合研究以及在酵母和产黄青霉中的下游分析，使得能够鉴定出一种MAT1-1-1 DNA结合基序，并在真子囊菌中高度保守。我们的研究为更全面地理解所有真菌中发育和代谢的这些主控开关铺平了道路，并为优化真菌高产菌株开辟了新的途径。
