Mining an O-methyltransferase for de novo biosynthesis of physcion in Aspergillus nidulans,Applied Microbiology and Biotechnology

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Mining an O-methyltransferase for de novo biosynthesis of physcion in Aspergillus nidulans
Applied Microbiology and Biotechnology ( IF 3.9 ) Pub Date : 2023-01-17 , DOI: 10.1007/s00253-023-12373-y
Yongpeng Yao ₁ , ErLan Yang ₂ , Yuanyuan Pan ₁ , Xian Shu ₁ , Gang Liu _{1,

3}

Affiliation

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

Graphical abstract

中文翻译：

挖掘用于构巢曲霉中大黄素从头生物合成的 O-甲基转移酶

摘要

Physcion 是一种天然蒽醌类化合物，因其对植物病害的出色预防而被注册为新型植物源性杀菌剂。然而，目前植物提取生产大黄素的现状限制了其产量推广和应用。在这里，大黄素生物合成中的一对聚酮合酶 (PKS) 被用作探针来挖掘负责大黄素生物合成的潜在 O-甲基转移酶 (OMT)。使用开采的 OMT 的系统发育分析进一步细化揭示了一个独特的 OMT (AcOMT) 具有将甲基转移到大黄素的 C-6 羟基以形成大黄素的能力。通过引入AcOMT，我们成功地获得了构巢曲霉中大黄素的从头生产. 通过表达来自不同真菌的脱羧酶基因，进一步合理地设计了physcion生物合成途径。最后，通过增加 S-腺苷甲硫氨酸的供应，在摇瓶发酵中大黄素甲醚的效价达到 64.6 mg/L。我们的工作为physcion生物合成提供了一种天然的O-甲基转移酶，并为通过可持续途径进一步提高physcion的生产奠定了基础。