Transcriptional Differences Guided Discovery and Genetic Identification of Coprogen and Dimerumic Acid Siderophores in Metarhizium robertsii

Abstract

Siderophores are small molecular iron chelators and participate in the multiple cellular processes in fungi. In this study, biosynthesis gene clusters of coprogens and dimerumic acids were identified by transcriptional level differences of genes related to iron deficiency conditions in Metarhizium robertsii. This leads to the characterization of new coprogen metachelin C (1) and five known siderophores metachelin A (2), metachelin A-CE (3), metachelin B (4), dimerumic acid 11-mannoside (5), and dimerumic acid (6). The structure of metachelin C (1) was elucidated by NMR spectroscopy and HR-ESI-MS analysis. Genetic deletions of mrsidA, and mrsidD abolished the production of compounds 1–6 that implied their involvement in the biosynthesis of coprogen and dimerumic acid. Interestingly, NRPS gene mrsidD is responsible for biosynthesis of both coprogen and dimerumic acid, thus we proposed plausible biosynthetic pathways for the synthesis of coprogen and dimerumic acid siderophores. Therefore, our study provides the genetic basis for understanding the biosynthetic pathway of coprogen and dimerumic acid in Metarhizium robertsii.

Elucidating the molecular programming of a nonlinear non-ribosomal peptide synthetase responsible for fungal siderophore biosynthesis

“…The hydroxamate-containing units, l -AHO and cis -/ trans -AMHO, are enzymatically incorporated into chemical scaffolds and define two separate families of hydroxamate siderophores. These include the depsipeptides, typified by fusarinine C (FSC) ( 1 ) 9 and coprogen 10 , 11 , which utilise either cis- or trans- AMHO as monomeric units and are excreted primarily to capture ferric iron (Fig. 1a ) 12 .…”

Unlocking the Siderophore Biosynthesis Pathway and Its Biological Functions in the Fungal Insect Pathogen Beauveria bassiana

“…In Metarhizium robertsii (a sister entomopathogenic fungus), MrSidD is responsible for the production of coprogen and dimerumic acid. 40 This finding suggests the complexity of siderophore synthesis pathways in different filamentous fungi. Together, B. bassiana has a siderophore biosynthetic pathway similar to that in Aspergillus species, and the "core" genes of this pathway differentially contribute to production of diverse siderophores.…”

Trichoderma: A Review of Its Mechanisms of Action in Plant Disease Control

“…Microbial siderophores' chemical composition and iron-binding characteristics are commonly separated into catecholate, hydroxamate and carboxylate [80]. Coprogens, ferrichrome, and fusarinines are hydroxamate siderophores widely found in fungi and have a standard architectural arrangement of N5-acyl-N5-hydroxyornithine [81,82]. Figure 1 explains how siderophores bind to Fe 3+ and convert it to Fe 2+ , a soluble form that plants and microbes may easily absorb [83].…”