Abstract
Physcion is one of natural anthraquinones, registered as a novel plant-derived fungicide due to its excellent prevention of plant disease. However, the current production of physcion via plant extraction limits its yield promotion and application. Here, a pair of polyketide synthases (PKS) in emodin biosynthesis were used as probes to mining the potential O-methyltransferase (OMT) responsible for physcion biosynthesis. Further refinement using the phylogenetic analysis of the mined OMTs revealed a distinct OMT (AcOMT) with the ability of transferring a methyl group to C-6 hydroxyl of emodin to form physcion. Through introducing AcOMT, we successfully obtained the de novo production of physcion in Aspergillus nidulans. The physcion biosynthetic pathway was further rationally engineered by expressing the decarboxylase genes from different fungi. Finally, the titer of physcion reached to 64.6 mg/L in shake-flask fermentation through enhancing S-adenosylmethionine supply. Our work provides a native O-methyltransferase for physcion biosynthesis and lays the foundation for further improving the production of physcion via a sustainable route.
Key points
• Genome mining of the native O-methyltransferase responsible for physcion biosynthesis
• De novo biosynthesis of physcion in the engineered Aspergillus nidulans
• Providing an alternative way to produce plant-derived fungicide physcion
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Acknowledgements
This study was supported by the National Key Research and Development Program (2021YFC2100600) and the National Natural Science Foundation of China (grant no. 32001036).
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YY and EY designed and performed main experiments and data analyses. YY performed data curation and writing of the original draft. YP helped to revise the manuscript and gave valuable advices on experimental design and data analyses. XS conducted experiments. GL did conceptualization and writing review and editing. All authors read and approved the manuscript.
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YY, YP, and GL are inventors on a provisional patent application related to this work (no. CN202211098075.9, filed 8 September 2022). All other authors declare no competing interests.
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Yao, Y., Yang, E., Pan, Y. et al. Mining an O-methyltransferase for de novo biosynthesis of physcion in Aspergillus nidulans. Appl Microbiol Biotechnol 107, 1177–1188 (2023). https://doi.org/10.1007/s00253-023-12373-y
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DOI: https://doi.org/10.1007/s00253-023-12373-y