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

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.

Automated summary

In this study, biosynthesis gene clusters of coprogens and dimerumic acids were identified in Metarhizium robertsii by analyzing transcriptional level differences of related genes under iron deficiency conditions. The genes mrsidA and mrsidD were found to be involved in the biosynthesis of coprogen and dimerumic acid, as genetic deletions of these genes led to decreased production of the compounds. The NRPS gene mrsidD was shown to be responsible for the biosynthesis of both coprogen and dimerumic acid siderophores, suggesting a plausible biosynthetic pathway for these compounds.