**6. Biosynthetic pathways for relevant bioactive phytochemicals**

#### **6.1 Bixin biosynthesis**

The biosynthesis of the apocarotenoid ester bixin from lycopene requires four enzymatic reactions (**Figure 6**). The first enzymatic reaction of bixin biosynthesis is the 5-6/5′-6′ oxidative cleavage of lycopene catalyzed by lycopene cleavage oxygenase to produce two sulcatone and one bixin aldehyde molecule. The second enzymatic reaction is the oxidative conversion of aldehyde into carboxylic acid groups in bixin aldehyde to produce norbixin by bixin aldehyde dehydrogenase. The third enzymatic reaction is the methylation of one norbixin carboxyl group to produce bixin by norbixin methyltransferase. This enzyme utilizes *S*-adenosyll-methionine as a methyl-group donor. Finally, the last biochemical reaction is the methylation of one bixin carboxyl group to produce bixin dimethyl ester by bixin methyltransferase, using *S*-adenosyl-l-methionine as methyl-group donor [89–91].

#### **6.2 Linalool biosynthesis**

The fundamental building blocks in plants for terpenoid production, i.e., isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), are generated via two independent pathways, namely, 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway and the mevalonate acid (MVA) pathway [92, 93]. The plastid terpenes are formed exclusively via the MEP pathway; however, sterols are biosynthesized via MVA pathway in the cytoplasm and mitochondria [94, 95]. Radiolabeling studies in the early 1970s showed that in *Cinnamomum camphora* the biosynthesis of linalool is accomplished via the MVA pathway [96]. Nevertheless, recent transcriptome analysis of leaves in two chemotypes of *C. camphora* showed that both pathways provide the biosynthetic precursors IPP and DMAPP for the main monoterpenes (i.e., linalool and borneol) synthesis [97]. The balance of IPP/ DMAPP is controlled by type 1 and type 2 isopentenyl diphosphate:dimethylallyl diphosphate isomerase, which reversibly converts IPP to DMAPP [98, 99]. Further, IPP and DMAPP are condensed by geranyl diphosphate synthase and isopentenyl diphosphate to produce geranyl diphosphate by geranyl diphosphate synthase. Finally, geranyl diphosphate is transformed in linalool by the action of linalool synthase (**Figure 7**).

#### **6.3 Quercetin biosynthesis**

A bioactive phytochemical that is biosynthesized through the phenylpropanoid pathway [100]. The initial reactions transform phenylalanine into 4-coumaroyl-CoA, which enters into the flavonoid biosynthesis pathway (**Figure 8**). The first committed enzyme in the flavonoid pathway, chalcone synthase, uses malonyl-CoA and 4-coumaroyl-CoA as substrates to produce naringenin chalcone. This metabolic

**Figure 6.**  *Biosynthetic pathway for bixin.* 

intermediary is converted to (+)-dihydrokaempferol by the action of two enzymes, one isomerase and one dioxygenase, respectively. Next, (+)-dihydrokaempferol quercetin is biosynthesized by two alternative and consecutive enzymatic reactions: first, enzymes (+)-dihydrokaempferol 3′-hydroxylase and quercetin synthase produce (+)-taxifolin as a metabolic intermediary, and, second, enzymes dihydrokaempferol synthase and kaempferol monooxygenase produce kaempferol as a metabolic intermediary [101].

*Medicinal Plants of the Peruvian Amazon: Bioactive Phytochemicals, Mechanisms of Action… DOI: http://dx.doi.org/10.5772/intechopen.82461* 

**Figure 7.** 

*Biosynthetic pathway for linalool through the MEP pathway.* 

## **7. Strategies for the sustainable use of medicinal plants**

To date, the research contributions of the Peruvian Amazon to ethnopharmacology have been very limited, and data are still fragmentary and dispersed. Consequently, to ensure a sustainable economic development, we need to obtain a competitive advantage based on our medicinal plant resources. To achieve these goals, we must formulate appropriate strategies based on solid scientific knowledge. First, we need to record the millenary knowledge of folk medicine practiced by the total ethnic groups of the Peruvian Amazon. Second, based on this information, we

**Figure 8.**  *Biosynthetic pathway for quercetin.* 

 should construct a complete catalog of known medicinal plants with correct taxonomic identifications. Third, an enriched germplasm bank of medicinal plants should be established with accessions of several sites of the Peruvian Amazon. Fourth, the bioactivity of extracts/bio-guided isolated and purified phytochemicals with a battery of *in vitro* and *in vivo* standardized bioassays against multiple diseases (e.g., diabetes, cancer, bacterial infections, etc.) should be established. Fifth, multiomics approaches such as genomics, transcriptomics, proteomics, and metabolomics should be performed to identify key genes, enzymes, and metabolic pathways responsible for the biosynthesis of promising bioactive phytochemicals. Sixth, in the short term, a web-based computerized database to facilitate storage, management, transfer and

*Medicinal Plants of the Peruvian Amazon: Bioactive Phytochemicals, Mechanisms of Action… DOI: http://dx.doi.org/10.5772/intechopen.82461* 

exchange, and analysis of the data by researchers, planners, and other interested users should be developed and made freely available. Finally, the availability of this basic scientific information could support the development of genetic improvement programs for medicinal plants and allow a boost of biotechnological applications, based on synthetic biology tools and using bacterial, microalgal, and several other cell-/tissue-based platforms for the production of phytochemical compounds of interest, thus preventing overexploitation and species extinction of medicinal plants.
