Biosynthesis of Gossypol

Abstract

Abstract Based on the previous observations that gossypol is biosynthetically formed from acetate, and from the location of the incorporated 14C atoms, gossypol biosynthesis via the isoprenoid pathway has been postulated. To support this hypothesis, the incorporation of mevalonate-2-14C (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-2-14C are stereospecifically incorporated into 1 molecule of gossypol. The monoterpene alcohols, geraniol-2-14C and nerol-2-14C, 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-2-14C. 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, farnesyl-2-14C-PP, was 4 times as efficient as substrate compared to the trans-cis isomer. In constrast, the incorporation of trans-trans- and cis-trans-farnesyl-2-14C-PP into gossypol was negligible. From the labeling pattern of gossypol synthesized from mevalonate-2-14C, neryl-2-14C-PP, and trans-cis-farnesyl-2-14C-PP, it is proposed that gossypol is produced by a specific cyclization of cis-cis-farnesyl pyrophosphate.