Haplotype-resolved genome of Agastache rugosa (Huo Xiang) provides insight into monoterpenoid biosynthesis and gene cluster evolution

Abstract Monoterpenoids are small volatile molecules produced by many plants that have applications in consumer products and healthcare. Plants from the mint family (Lamiaceae) are prodigious producers of monoterpenoids, including a chemotype of Agastache rugosa (Huo Xiang), which produces pulegone and isomenthone. We sequenced, assembled and annotated a haplotype-resolved chromosome-scale genome assembly of A. rugosa with a monoterpene chemotype. This genome assembly revealed that pulegone biosynthesis genes are in a biosynthetic gene cluster, which shares a common origin with the pulegone gene cluster in Schizonepeta tenuifolia. Using phylogenetics and synteny analysis, we describe how the clusters in these two species diverged through inversions and duplications. Using Hi-C analysis, we identified tentative evidence of contact between the pulegone gene cluster and an array of pulegone reductases, with both regions also enriched in retrotransposons. This genome and its analysis add valuable and novel insights to the organization and evolution of terpenoid biosynthesis in Lamiaceae.