Biosynthesis of Gossypol

Based on the previous observations that gossypol is biosynthetically formed from acetate, and from the location of the incorporated 1% atoms, gossypol biosynthesis via the isoprenoid pathway has been postulated. To support this hypothesis, the incorporation of mevalonate-2J4C (a key intermediate in the isoprenoid pathway) into gossypol as well as the distribution of the radioactivity in the gossypol molecule was studied. The results showed that 6 molecules of mevalonate-2J4C are stereospecifically incorporated into 1 molecule of gossypol. The monoterpene alcohols, geraniol2J4C and nerol-Z-W, were chemically synthesized and the incorporation of their respective pyrophosphate ester into gossypol was tested. The incorporation of geranyl-2-14C pyrophosphate into gossypol was equal to the incorporation of mevalonate-2-14C, whereas neryl-2-14C pyrophosphate was utilized twice as efficiently as mevalonate-2-W. The location of the 14C atoms of these substrates in the gossypol molecule was consistent with the isoprenoid pathway. Similarly, the cis-cis isomer of the sesquiterpene alcohol, farnesylZ-14C-PP, was 4 times as efficient as substrate compared to the trans-cis isomer. In constrast, the incorporation of