Uncovering a miltiradiene biosynthetic gene cluster in the Lamiaceae reveals a dynamic evolutionary trajectory

The spatial organization of genes within plant genomes can drive evolution
of specialized metabolic pathways. In this study we investigated the
origin and subsequent evolution of a diterpenoid biosynthetic gene cluster
(BGC) present throughout the Lamiaceae (mint) family. Terpenoids are
important specialized metabolites in plants with diverse adaptive
functions that enable environmental interactions, such as chemical
defense. Based on core genes found in the BGCs of all species examined
across the Lamiaceae, we predict a simplified version of this cluster
evolved in an early Lamiaceae ancestor. The current composition of the
extant BGCs highlights the dynamic nature of its evolution. We elucidate
the terpene backbones made by the Callicarpa americana BGC enzymes,
including miltiradiene and the novel terpene (+)-kaurene, and show
oxidization activities of BGC cytochrome P450s. Our work reveals the fluid
nature of BGC assembly and the importance of genome structure in
contributing to the origin of novel metabolites.

植物基因组内基因的空间排布可驱动特化代谢通路的演化。本研究针对广泛分布于唇形科（Lamiaceae，俗称薄荷科）的二萜生物合成基因簇（biosynthetic gene cluster, BGC）的起源及其后续演化过程展开系统探究。萜类化合物是植物中一类重要的特化代谢物，具备多样的适应性功能以介导环境互作，例如化学防御。基于对唇形科所有已检测物种BGC中核心基因的分析，我们推测该基因簇的简化版本曾在唇形科的早期祖先类群中演化形成。现存BGC的组成结构凸显了其演化过程的动态性。我们解析了美洲紫珠（Callicarpa americana）BGC编码酶所合成的萜类骨架，包括丹参二烯（miltiradiene）与新型萜类化合物(+)-贝壳松烯（(+)-kaurene），并阐明了该BGC中细胞色素P450（cytochrome P450）的氧化催化活性。本研究揭示了BGC组装的动态流动性特征，以及基因组结构对于新型代谢物起源的重要贡献。