CYP76BK1 orthologs catalyze furan and lactone ring formation in clerodane diterpenoids across the mint family

• DOI: 10.1111/tpj.17031
• Publication Date: 2024-09-14T17:59:12Z
• Authors: Nicholas J. Schlecht; Emily R. Lanier; Trine B. Andersen; Julia Brose; Daniel Holmes; Björn R. Hamberger
• Keywords: Furan

SUMMARY The Lamiaceae (mint family) is the largest known source of furanoclerodanes, a subset clerodane diterpenoids with broad bioactivities including insect antifeedant properties. Ajugoideae subfamily, in particular, accumulates significant numbers structurally related furanoclerodanes. biosynthetic capacity for formation these retained across most subfamilies, early‐diverging Callicarpoideae which forms sister clade to rest Lamiaceae. VacCYP76BK1 , cytochrome P450 monooxygenase from Vitex agnus‐castus was previously found catalyze proposed precursor furan and lactone‐containing labdane diterpenoids. Through transcriptome‐guided pathway exploration, we identified orthologs Ajuga reptans Callicarpa americana. Functional characterization demonstrated that both could oxidative cyclization backbones yield ring. Subsequent investigation revealed total 10 CYP76BK1 six subfamilies. analysis available chromosome‐scale genomes, four members as syntelogs within conserved syntenic block divergent This suggests an evolutionary lineage predates speciation affirmed conservation function, all catalyzed ring formation. Additionally, some yielded two novel lactone moieties. presence subfamilies closely overlaps distribution reported Together, activities here support their central role furanoclerodane biosynthesis family. Our findings lay groundwork biotechnological applications harness economic potential this promising class compounds.