## 6 Phytoelxin Engineering: Where Plant and Human Interests do not Meet  
As some phytoalexins, especially cottonseed and potato phytoalexins, display a certain level of toxicity for humans, there was a crucial interest in engineering those plants for abolishing accumulation of these undesirable compounds. Genetic manipulation of plants for technological applications can affect phytoalexin expression. This is the case with potatoes which produce a number of antinutritional phytoalexins such as the steroid glycoalkaloids \(\alpha\)-solanine and \(\alpha\)-chaconine [168] (Figure 2). Potatoes genetically modified with an antisense potato invertase gene, exhibited a modified phytoalexin profile regarding glycoalkaloids. Specifically, transgenic lines were obtained by introducing a potato acid invertase gene sequence in antisense orientation driven by a patatin promoter and subtended by the _Agrobacteriumum_-derived napaline synthase terminator. This was done to genetically manipulate through a reduction in the amount of invertase, the accumulation of reducing sugars responsible for subsequent browning problems during cooking at high temperatures. Such transformation namely decreased glycoalkaloid accumulation in potatoes _vs._ controls. It was speculated that diminutions in the carbohydrate pool in antisense invertase lines may reduce the UDP-glucose:solanidine glucosyltransferase and the UPD-galactose:solanidine galactosyltransferase-mediated conversion of solanidine to \(\gamma\)-chaconine and \(\gamma\)-solanidine, respectively, decreasing the amounts of the toxic glycoalkaloids \(\alpha\)-chaconine and \(\alpha\)-solanidine. Modifications of these toxic secondary metabolites in potatoes were related to a direct effect of the transgene rather than to interactions of the plant with its environment. Gossypol and its congeners are dimeric sesquiterpene phytoalexins of the cadinane family from cotton (_Gossypium hirsutum_) deriving from the plastidic methylerythritol phosphate (GAP-pyruvate) pathway [161]. The latter leads to two C\({}_{5}\) units, respectively isopentenyl-pyrophosphate (IPP) and its isomer dimethylallyl-pyrophosphate (DMAPP). Condensation of these two C\({}_{5}\) units and larger IPP- and DMAPP-derived building blocks such as the C\({}_{10}\) unit, geranyl pyrophosphate (GPP), the C\({}_{15}\) unit, farnesyl pyrophosphate (FPP) and the C\({}_{20}\) unit, geranylgeranyl pyrophosphate (GGPP), yields monoterpenes, sesquiterpenes (such as gossypol), triterpenes (steroids), tetraterpenes (carotenoids) and diterpenes. The starter of the biosynthetic route to gossypol is farnesyl diphosphate (FPP) (Figure 6). In cotton, (+)-\(\delta\)-cadinene synthase (CDNS) catalyzes the cyclization of \(E\),_Z_-FPP to (+)-\(\delta\)-cadinene, involving isomerization of FPP to a nerolidyll intermediate, the cyclization of which leads to a _cis_-germacradienyl cation. This is followed by 1,3-hydride shift, cyclization to a cadinanyl cation and deprotonation to form (+)-\(\delta\)-cadinene [169,170]. CDNS catalyzes the first committed step in the route of the cadinane sesquiterpenoids from FPP, making this enzyme a crucial control component for gossypol engineering (Figure 6). According to the works of [PERSON] and colleagues [171,172], four cDNAs of _cdn_ synthase have been isolated from _Gossypium arboreum_, _i.e._, _cdn_1-C1, _cdn_1-C14, _cdn_1-A and _cdn_1-C2. Gossypol plays a role as a phytoalexin produced in response to the fungal pathogen _Verticillium dahlia_ [PERSON] and to bacterial blight, caused by _Xanthomonas campestris_ pv. _malvaccarum_ ([PERSON] [PERSON]. Beside its presence in the epidermis and hairs of developing roots together with its storage within the very typical lysigenous gossypol glands in the foliage, gossypol is the main cadinane sesquiterpen in developing and mature seeds as well as in the cottonseed glands. Gossypol is known to be toxic and to have antifertility effects on animals and humans ([173] and referencestherein) and must be removed from cottonseed oil prior to human consumption.