# Unraveling the Complexity of Plant Trichomes: Models, Mechanisms, and Bioengineering Strategies
## 4 Glandular Secretory Trichomes (GSTs): Natural Biofactories
### Secondary Metabolite Synthesis in GSTs  
As biosynthetic hubs, GSTs produce and secrete a variety of volatile and non-volatile substances, such as terpen, phenolics, lipids, sugars, and alkaloids. Artemisinin and  
Figure 2: The morphology of glandular secretory trichomes in different species. GSTs of (**A**) _Cantabis sativa_[37], (**B**) _Solanum lycopersicum_, (**C**) _Artemisia annua_, (**D**) _Thymus vulgaris_[35], (**E**) _Cucumis sativus_[33], different types of trichomes marked by red, blue, green asterisks, (**F**) _Phillyna latifolia_[32], (**G**,**H**) _Lonicera japonica_[36], and (**I**) _Schizonepeta tenuifolia_[18]. cannabinoids are well-known secondary metabolites derived from GSTs for their significant medicinal effects [12; 17]. Cannabinoids are terpenophenolic compounds that constitute the primary active constituents of _Cannabis_. These compounds have been shown to possess anti-epileptic, anti-depressant, neuroprotective, anti-inflammatory, analgesic, and anti-tumor properties [28; 29]. There are four key stages in the biosynthesis of cannabinoids: hexanoate biosynthesis, 2-methylerythritol-4-phosphate (MEP) biosynthesis, geranylpyrophosph (GPP) biosynthesis, and cannabinoid biosynthesis. The cannabinoid pathway utilizes products synthesized from the preceding three pathways as substrates. Specifically, olivetol synthase (OLS) catalyzes the condensation of hexanoyll-CoA (derived from the hexanoate pathway) with malonyl-CoA to form olivetolic acid (OA). In the next step, olivetolic acid undergoes prenylation, resulting in cannabigerolic acid (CBGA) by combining with GPP [38]. It is believed that this step is the most crucial in the process of producing cannabinoids. Additionally, CBGA serves as the central precursor and is specifically catalyzed by enzymes found in GSTs: tetrahydroocannabinolic acid synthase (THCAS), cannabidiolic acid synthase (CBDAS), and cannabichromeic acid synthase (CBCAS). This catalysis produces tetrahydroocannabinolic acid (THCA), cannabidiolic acid (CBDA), and cannabichromeic acid (CBCA), respectively. Finally, these acidic cannabinoids undergo non-enzymatic decarboxylation (typically through heating) to yield the neutral forms: \(\Delta^{9}\)-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabichromee (CBC). Malaria, known as one of the most life-threatening diseases on earth, is an infectious disease caused by Plasmodium parasites. It is transmitted to humans through the bites of infected female Anopheles mosquitoes. Artemisinin, a sesquiterpene lactone compound, was first discovered and extracted from the plant _Artemisia annua_ in 1972 by [PERSON], based on traditional Chinese medicine knowledge [39]. Artemisinin-based combination therapies (ACTs) have been recommended by the World Health Organization (WHO) as the most effective treatment for malaria at present [40]. Artemisinin is synthesized in subapical and apical cells, and it accumulates in the subepidermal space surrounding wax vesicles. Artemisinin's biosynthetic pathway has been extensively investigated over the past decade. Artemisinin is synthesized via the isoprenoid biosynthetic pathway, which utilizes farnesyl pyrophosphate (FPP) and its precursor, isopenenyl diphosphate (IPP). In plants, IPP is produced through two distinct pathways: the cytoplasmic mevalonate (MVA) pathway and the plastid-localized methylerythritol phosphate (MEP) pathway. Amorpha-4,11-diene synthase (ADS) catalyzes the cyclization of FPP to form amorpha-4,11-diene [41], which is recognized as the first committed step in artemisinin biosynthesis. Amorpha-4,11-diene undergoes three sequential hydroxylations catalyzed by the cytochrome P450 multifunctional oxidase CYP71 AV1, yielding artemisinin alcohol, artemisinin aldehyde, and (finally) artemisinin acid [42]. Artemisinic aldehyde is then reduced by artemisinin aldehyde \(\Delta\)11(13) reductase (DBR2) to form dihydroartemisinic aldehyde. This intermediate is oxidized by aldehyde dehydrogenase 1 (ALDH1) to produce dihydroartemisinic acid, the primary precursor of artemisinin.