Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
J Biol Chem. 2019 Oct 18;294(42):15193-15205. doi: 10.1074/jbc.RA119.010454. Epub 2019 Sep 3.
As a means to maintain their sessile lifestyle amid challenging environments, plants produce an enormous diversity of compounds as chemical defenses against biotic and abiotic insults. The underpinning metabolic pathways that support the biosynthesis of these specialized chemicals in divergent plant species provide a rich arena for understanding the molecular evolution of complex metabolic traits. Rosmarinic acid (RA) is a phenolic natural product first discovered in plants of the mint family (Lamiaceae) and is recognized for its wide range of medicinal properties and potential applications in human dietary and medical interventions. Interestingly, the RA chemotype is present sporadically in multiple taxa of flowering plants as well as some hornworts and ferns, prompting the question whether its biosynthesis arose independently across different lineages. Here we report the elucidation of the RA biosynthetic pathway in (desert bells). This species represents the borage family (Boraginaceae), an RA-producing family closely related to the Lamiaceae within the Lamiids clade. Using a multi-omics approach in combination with functional characterization of candidate genes both and , we found that RA biosynthesis in involves specific activities of a BAHD acyltransferase and two cytochrome P450 hydroxylases. Further phylogenetic and comparative structure-function analyses of the RA biosynthetic enzymes clearly indicate that RA biosynthesis has evolved independently at least twice in the Lamiids, an exemplary case of chemotypic convergence through disparate evolutionary trajectories.
为了在充满挑战的环境中维持其固着的生活方式，植物产生了大量的化合物作为抵御生物和非生物侵害的化学防御。支持这些特殊化学物质在不同植物物种中生物合成的基础代谢途径，为理解复杂代谢特征的分子进化提供了一个丰富的领域。迷迭香酸（RA）是一种酚类天然产物，最初在薄荷科（唇形科）植物中发现，因其广泛的药用特性和在人类饮食和医学干预中的潜在应用而受到认可。有趣的是，RA 化学型在多个开花植物类群以及一些角苔和蕨类植物中零星存在，这引发了一个问题，即其生物合成是否在不同的谱系中独立出现。在这里，我们报告了迷迭香酸生物合成途径在 （沙漠铃铛）中的阐明。该物种代表紫草科（紫草科），是一种产生迷迭香酸的科，与唇形科在 Lamiids 分支内密切相关。我们采用多组学方法，结合对候选基因的功能特征进行了功能表征，发现 中的 RA 生物合成涉及 BAHD 酰基转移酶和两种细胞色素 P450 羟化酶的特定活性。对 中 RA 生物合成酶的进一步系统发育和比较结构-功能分析清楚地表明，RA 生物合成在 Lamiids 中至少独立进化了两次，这是通过不同进化轨迹趋同的典型案例。
