Capsidiol

Capsidiol is produced in the pepper fruit Capsicum annuum or tobacco Nicotiana tabacum after infection by the oomycete water-mold Phytophthora capsici. In pepper or tobacco fields, the oomycete is soil-borne and initially infects roots, collars and lower leaves.  Sporangia are moved within fields by contact with field equipment, clothing, gloves, tools etc. and initial infections spread zoospores through splashing of water from irrigation or rain.[3]  Initial responses to infection include production of radical oxygen species, including H₂O₂.[4]  Exogenous treatment with H₂O₂ alone has been shown to induce capsidiol production.[4] Capsidiol production is then increased in response to radical oxygen species production.

Capsidiol is a bicyclic terpene that is biosynthetically derived from the mevalonate pathway via farnesyl pyrophosphate (FPP).  The E,E-farnesyl cation is first created by the loss of pyrophosphate.  Kinetic studies have indicated that turnover appears to be limited by a chemical step after the initial loss of pyrophosphate.[5]  Crystal structures of recombinant tobacco 5-epi-aristolochene synthase (TEAS), alone and also complexed with two FPP analogues have been reported and analyzed to suggest the following mechanism of biosynthesis.[6]  The E,E-farnesyl cation undergoes cyclization to form the germacryl cation. The second ring closure gives the bicyclic eudesmyl cation, which is stabilized by various dipole interactions, then H-2 migrates to C-3 producing a tertiary cation at C-2 (farnesyl numbering).[5]  Production of 5-epi-aristolochene from FPP by 5-epi-aristolochene 3-hydroxylase, a sesquiterpene cyclase, is considered the critical step in capsidiol biosynthesis.[1]  Aristolochene synthase enzymes from Penicillium roqueforti, Nicotiana tabacum have been purified and their crystal structures have been reported suggesting different steriochemistries for aristolochene.[5][6]  Penicillium roqueforti's enzyme appears to synthesizes aristolochene by way of (S)-germacrene A , however, the Nicotiana tabacum enzyme 5-epi-aristolochene synthase produces the diastereoisomeric product by way of (R)-germacrene A.[5]