Biosynthesis of Polycyclic Natural Products from Conjugated Polyenes via Tandem Isomerization and Pericyclic Reactions.
Kanji NiwaMasao OhashiKaili XieChen-Yu ChiangCooper S JamiesonMichio SatoKenji WatanabeFang LiuKendall N HoukYi TangPublished in: Journal of the American Chemical Society (2023)
We report biosynthetic pathways that can synthesize and transform conjugated octaenes and nonaenes to complex natural products. The biosynthesis of (-)-PF1018 involves an enzyme PfB that can control the regio-, stereo-, and periselectivity of multiple reactions starting from a conjugated octaene. Using PfB as a lead, we discovered a homologous enzyme, BruB, that facilitates diene isomerization, tandem 8π-6π-electrocyclization, and a 1,2-divinylcyclobutane Cope rearrangement to generate a new-to-nature compound.