Metabolic feedback signals controlling transcription: exploring pathogen induced biosynthesis of indole-glucosinolates as a prototypic model

• Applicant: Professor Dr. Wolfgang Dröge-Laser
• Subject Area: Organismic Interactions, Chemical Ecology and Microbiomes of Plant Systems
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 537270401

How metabolic signals are generated, transmitted and sensed to ultimately impact transcription is largely unknown in plants. In Brassicacea, the biosynthetic pathway leading to indolic glucosinolates (IGs) provides specialized metabolites, displaying profound ecological functions, as they protect against herbivores and microbial pathogens, perform as allelopathic compounds or act in sulfur storage. To accomplish a controlled metabolic flux, the complex IG biosynthetic pathway is highly coordinated, particularly on the level of transcription. Transcription factors of the MYB, MYC and ERF families have been well-described to coordinate transcription of the IG pathway genes. Particularly, MYB51 is a central activator of the upstream section of the IG biosynthetic pathway, whereas specific ERFs control pathogen-inducible downstream genes. It is tempting to propose metabolic feed-back control to coordinate the flux through this pathway, however, no mechanisms have been elucidated, yet. Here, we focus on root derived IGs, which effectively defend Arabidopsis plants against the vascular fungal pathogen Verticillium longisporum. Our previous work on this root-pathogen interaction has gained three novel findings: (1) Redundantly acting group IXb ERFs upregulate the pathogen-induced downstream IG pathway genes and simultaneously feedback to transcriptional activation of MYB51 by directly targeting its promoter, (2) MYB51 is activated by MAP kinase signaling in a yet uncharacterized manner, and (3) overexpression of a single bottleneck-enzyme of the downstream IG biosynthetic pathway (CYTOCHROME P450 81F2, CYP81F2) leads to increased IG content, enhanced fungal resistance and transcriptional upregulation of MYB51. We therefore propose that signals derived from the CYP81F2 enzyme/gene facilitate feedback control on MYB51 to coordinate metabolic flux. These findings provide a valuable entry point to study a prototypic example of metabolic sensing/signaling in plants. Two work packages will focus on the function of MYB51 in pathogen induced IG gene regulation by (A) genome-wide identification of MYB51 direct target genes using ChIPseq and (B) analyzing how MAP-kinase signaling is controlling MYB51 function. Workpage (C) will systematically define the CYP81F2-derived signals feeding back on MYB51 transcription. Potential candidate signals, such as metabolites, RNAs or moonlighting of the CYP81F2 protein in the nucleus will be functionally characterized. Taken together, research on metabolite signaling/sensing to control transcription in plants is lacking behind. Nevertheless, this topic is essential for basic understanding of metabolic pathway control as well as for bioengineering purposes. Due to the profound background knowledge, the IG pathway provides an excellent prototypic model system to address this topic.

• DFG Programme: Research Grants