# Lavandula Species, Their Bioactive Phytochemicals, and Their Biosynthetic Regulation
## 5 Biosynthesis Regulation of Lavelender Bioactive Phytochemicals
### Gene-Based Regulation of Lamiaceae Species Secondary Metabolites  
Plants are highly diverse in their chemical and metabolic profiles. In the case of lavender and other species in the _Lamiaceae_ family, they have evolved to produce large amounts of terpenoid compounds. This diversity is a result of their adaptation to different environmental conditions throughout the course of evolution and was enabled mainly via the subfunctionalization or neofunctionalization of genes previously duplicated in the events such as small-scale gene duplication (e.g., tandem duplication) or whole genome duplication (WGD) [81]. Enzyme promiscuity (the ability of enzymes to catalyze multiple reactions) and changes in substrate specificity play a role in the metabolic divergence seen in plants [82]. Nonhomologous genes, which encode enzymes involved in the same metabolic pathway are often physically grouped in certain regions of the genome in the form of biosynthetic gene clusters. This enables them to follow similar expression patterns and facilitates coniheritance. The dynamic evolution of genes within these clusters leads to an expansion of the functional diversity of their products [83]. The mechanisms behind the formation of these clusters are not fully understood, but one possible explanation is through the functional divergence of local duplications [84]. Such metabolic blocks were also characterized for genes involved in terpenoid biosynthesis [85; 86; 87]. In lavender, clusters of _TPS-TPS_ (terpene synthases), _TPS-BAHD_, and _TPS-CYP450_ were observed. Overall, 34 out of 1181 metabolic clusters identified in lavender were potentially associated with terpenoid biosynthesis [68]. Phylotranscriptomic analyses revealed 28 putative WGDs across the _Lamiaceae_ species, with 18 of these WGDs inferred to have occurred within the _Nepetoideae_ subfamily. This correlates with the high number of species within this clade [88]. Analysis of the lavender genome revealed that after the core \(\gamma\) triplication, shared among all eudicots, two additional lineage-specific WGD events occurred. In the penultimate WGD event, which occurred \(\sim\)29.6 million years ago (MYA), 23.1% of the duplicated genes have been retained, while the last WGD event, dated to \(\sim\)6.86 MYA, retained 32.5% of duplicated genes. The KyotoEncyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis revealed that a number of these genes were linked to terpenoid metabolism and plant defence, indicating the importance of terpenoid metabolism in lavender [68]. Poor understanding of the genomic and transcriptomic traits underlying secondary metabolite production in lavender was caused by limited genomic data resources of lavender in comparison to other _Lamiaceae_ species. The first genes involved in terpenoid biosynthesis in lavender were identified using a homology-based PCR approach [89]. These genes encode for three terpene synthases (TPSs): (R)-limonene synthase (LaLIMS), (R)-linalo synthase (LaLINS), and trans-alpha-bergamotene synthase (LaBERS), and similar to their homologues [90], each of these genes is composed of six introns with varying lengths [89]. The first expressed sequence tag (EST) library of _L. angustifolia_ revealed numerous genes involved in the MVA or MEP pathway as well as genes for known prenyltransferases and TPSs ([PERSON] et al., 2010) [8]. Analysis of EST libraries then became a common approach for identifying new _TPS_ genes [7; 8; 91; 92; 93]. Many genes associated with terpenoid biosynthesis in lavender species were reported and identified, using the above-mentioned approaches or their combination, which enabled their cloning and further characterization, e.g., 1,8-cineole synthases (_CINS_), borneol dehydrogenase (_BDH_), 9-epi-caryophyllene synthase (_CPS_), lavandulyl diphosphate synthase (_LPPS_), alcohol acetyltransferasease-3/-4 (_AAT-3/4_), 3-carene synthase (_3 CARS_), and bornyl diphosphate synthase (_BPPS_) were identified in _L.