Golubova D, Salmon M, Su H, Tansley C, Kaithakottil G G, Linsmith G, Schudoma C, Swarbreck D, O'Connell M A, Patron N J
Engineering Biology, Earlham Institute, Norwich Research Park, Norwich, UK.
School of Chemistry, Pharmacy and Pharmacology, University of East Anglia, Norwich, UK.
Nat Commun. 2025 Jul 28;16(1):6941. doi: 10.1038/s41467-025-62269-w.
Plants have been central to traditional medicine for millennia, yet the precise metabolites responsible for their therapeutic properties often remain unidentified. In this work, we investigate the reported anti-inflammatory properties of Calendula officinalis (pot marigold), an ancient medicinal herb. We confirm C16-hydroxylated triterpenoids as key contributors to the anti-inflammatory activity of C. officinalis floral extracts and uncover a mechanism by which they act in modulating interleukin 6 release. Through biosynthetic pathway elucidation, we demonstrate that the oxidosqualene synthase catalysing the first committed step emerged early in Asteraceae evolution and identify residues governing product specificity. Further, we functionally characterise cytochrome P450s and acyltransferases responsible for downstream modifications. By reconstructing the complete biosynthetic pathway in the plant chassis Nicotiana benthamiana, we provide a basis for the future bioproduction of the anti-inflammatory components. Our work highlights how integrated studies of bioactivity and biosynthesis can unlock the therapeutic potential of medicinal plants.
几千年来，植物一直是传统医学的核心，但负责其治疗特性的精确代谢物往往仍未被鉴定出来。在这项工作中，我们研究了古老的药用植物金盏花（万寿菊）所报道的抗炎特性。我们确认C16-羟基化三萜类化合物是金盏花花提取物抗炎活性的关键贡献者，并揭示了它们调节白细胞介素6释放的作用机制。通过阐明生物合成途径，我们证明催化第一步关键反应的氧化鲨烯合酶在菊科植物进化早期就已出现，并鉴定了决定产物特异性的残基。此外，我们对负责下游修饰的细胞色素P450和酰基转移酶进行了功能表征。通过在植物底盘本氏烟草中重建完整的生物合成途径，我们为未来抗炎成分的生物生产提供了基础。我们的工作突出了生物活性和生物合成的综合研究如何能够释放药用植物的治疗潜力。
