## 1 Introduction  
Plant-derived medicinal natural products are important sources of medicines for treating a wide range of diseases. _Lithospermrum erythrorhizon_ Sieb. et Zucc, an important medicinal plant in East Asian and Western traditional medicine, can biosynthesize red naph-toquinone compounds, namely shikonin and its derivatives, in its root periderm [1]. These compounds have been shown to have anti-HIV [2], antioxidant [3], anti-inflammatory [4, 5], wound healing [6], and other pharmacological activities [7, 8, 9], as well as to trigger cancer cell apoptosis, making them yet another promising natural anti-tumor drug [10, 11]. Furthermore, these metabolites are widely used natural raw materials for making cosmetics and dyes that have a high market value. However, due to the difficulties of cultivating _L. erythrorhizon_ and the low amount of root periderm, plant-based production is seriously unable to meet the global demand. Despite the development of the chemical synthesis of shikonin, the yield is only 0.7%, involving 12 reaction steps, and the cost is relatively expensive, making it insufficient for industrial production [12; 13; 14]. Therefore, it is crucial to increase the production of shikonin and its derivatives by identifying key genes in the biosynthesis pathway, using strategies such as high-yield transgenic cell lines and synthetic biology, and utilizing the \"two-stage cultivation system\" to produce shikonin and its derivatives for _L. erythrorhizon_ cells [15; 16] and hairy roots [16; 17]. The biosynthetic pathway of shikonin and its derivatives has primarily been elucidated: geranyl pyrophosphate is synthesized via the mevalonate (MVA)/methylorbitol phosphate metabolic pathway [18] and _p_-hydroxybenzoic acid is synthesized via the phenylpropanol pathway [19] to form 3-geranyl-4-hydroxybenzoic acid under the catalysis of _p_-hydroxybenzoate geranyltransferase (PGT) [20; 21; 22]. The 3-geranyl-4-hydroxybenzoic acid is then catalyzed by geranylhydroquinone 3\"-hydroxyylase [23; 24], CYP76B101 [25], DSH1/DSH2 [26], LeSAT1 [27], LeAAT1 [27] and some unidentified enzymes to generate the final shikonin and its derivatives via a series of reactions including hydroxylation, oxidation, cyclization, acylation, etc. Since [PERSON] et al. [28] and [PERSON] et al. [29] discovered that mevinolin, a specific inhibitor of 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGR), inhibits 98% and 92.82% of the accumulation of shikonin and its derivatives in _L. erythrorhizon_ and _Arnebia euchroma_ suspension cells, respectively, and that the down-regulation of the _L. erythrorhizon_ geranyl diphosphate synthase (_LeGPPS_) gene also results in reduced shikonin production and a decreased expression of mevalonic acid and phenylpropanol pathway genes [30; 31], it has been widely believed that the MVA pathway serves as the primary source of the geranyl pyrophosphate required for the biosynthesis of shikonin and its derivatives. Additionally, as the most critical and first rate-limiting enzyme in the MVA pathway, HMGR can catalyze the conversion of one molecule of 3-hydroxy-3-methylglutary-CoA (HMG-CoA) and two molecules of triphosphopyridine nucleotide (NADPH) into mevalonate [32], which may have a significant and direct effect on the biosynthesis of shikonin and its derivatives. [PERSON]  
published HMM model (PF00368) (Figure 1A). All of these species could well represent the main taxa of plants and contained 10 lower plants, 4 Bryophytes, 3 Pteridophyta, 4 Gymnosperms, and 15 Angiosperms (1 basal angiosperm, 10 eudicots, and 4 monocots). More _HMGR_ family genes were found in vascular plants than in nonvascular plants. In the genomes of 10 species of Phycophyta, no _HMGR_ gene was identified in the genomes of seven species of Chlorophyta, and 1-2 _HMGR_ genes were identified in the genomes of three species of Charophyta (Table S1).