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Concise Biosynthesis of Phenylfuropyridones in Fungi |
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| Authors: | Dr Zhuan Zhang Tianzhang Qiao Prof Kenji Watanabe Prof Yi Tang |
| Institution: | 1. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095 USA
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095 USA;2. Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, CA, 90095 USA;3. Department of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan |
| Abstract: | Phenylfuropyridone natural products from fungi exhibit a range of antibacterial and cytotoxicity activities, and can potentiate azole antifungal compounds. We elucidated the biosynthetic pathway of compounds in the citridone family through heterologous reconstitution of the pfp pathway. We demonstrate that multiple members of this family can be accessed from a reactive ortho-quinone methide (o-QM) intermediate through electrocyclization, cycloisomerization, or conjugate addition. Formation of the quaternary carbon center in citridone B is catalyzed by an epoxide-forming P450 enzyme, followed by carbon skeletal rearrangement. Our results showcase how nature harvests the reactivities of an o-QM intermediate to biosynthesize complex natural products. |
| Keywords: | antimicrobial compounds biosynthesis P450 enzymes pyridones quinone methides |