## 1 Introduction  
Prenylation is one of the post-structural modifications essential for the increasing biological activities of several natural products [1]. Transferring the prenyl moieties onto the aromatic acceptor molecules often leds to prenylated derivatives with greatly improved therapeutic potency [2]. This process has become a new frontier for developing novel drugs and lead compounds in the pharmaceutical industry, especially for antimicrobial, antioxidant, anti-inflammatory, and anti-cancer agents [3, 4, 5]. Nevertheless, plant-based production of these valuable products is limited by finite resources, low yields, slow growth rates, seasonal dependency, and rare, or completely absent in some regions [6, 7]. Moreover, the chemozymatic and total synthesis of the prenylated products is rather difficult, as it is challenged by the structural complexity which requires multiple steps of the uncontrollable regio- and stereoselective prenylation, and expensive starting materials [8, 9]. Ferulenol (2), a C-3 farnessylated 4-hydroxycoumarin, is a major constituent in _Ferula communis_ (Giant fennel) which possesses many biological activities [5, 10]. According to previous studies, this compound exhibits cytotoxicity against various lines of cancer cells including human breast (MCF-7), colon (Caco-2), ovarian (SK-OV-3), and leukemic (HL- 60) in a dose-dependent manner, with the mode of action resembling paclitaxel (taxol) [11, 12]. Ferulenol (2) also exerts anti-cancer activity through the downregulation of Bcl2 protein along with upregulation of Bax protein in benzo[a]pyrene-induced lung cancer in a rat model [13]. This indicated ferulenol (2) as a pro-oxidant and chemotherapeutic agent and has been recognized as an interesting lead compound for anti-cancer semi-synthesis [13; 14]. In searching for the novel anticoagulant warfarin derivatives, ferulenol (2) exhibits higher activity than the warfarin drug (approximately 22 times) with lower toxicity [15; 16]. This compound also possesses antimycobacterial activity against fast-growing _Mycobacterium_ species [17]. Although chemical synthesis of this compound could be achieved by the reaction between 4-hydroxycoumarin sodium salt (4 HCNa) and all trans-farnesylchloride based on alkylation at the C-3 of coumarin [15], these processes are quite complicated, and the starting precursors are rather expensive. Engineering microbial cells as the in vivo prenylation system provides several advantages over the two existing methods, as microbes can be grown very fast in the noncomplex medium and can be easily extended to large-scale production [9; 18]. More importantly, microbes can supply various lengths of prenyl donors, e.g., dimethylallyl pyrophosphate (DMAPP, C5), geranyl pyrophosphate (GPP, C10), farnesyl pyrophosphate (FPP, C15), and geranylgeranyl pyrophosphate (GGPP, C20), through their inherent isoprenoid pathways [7; 19]. _E. coli_ solely synthesizes isoprenoids via the 1-deoxy-D-xylulose 5-phosphate (DXP) pathway (also known as non-mevalonate pathway), in which 1-deoxy-D-xylulose 5-phosphate synthase (DXS) is known as the first committing step enzyme that controls the metabolic flux of isoprenoids precursors [20; 21; 22; 23; 24]. In wild type _E. coli_, FPP serves as the key branching point in the synthesis of the vital molecules, i.e., heme O, ubiquinone, and peptidoglycan [25; 26; 27; 28]. Consequently, the metabolic flux of this precursor in _E. coli_ has been redirected towards taxadiene, carotenoids, and amorpha-4,11-diene through heterologous expression of various terpene synthases [29; 30; 31; 32; 33; 34]. In the last few years, using microorganisms as the prenylation systems for the production of hybrid molecules containing prenyl moieties has focused mainly on yeasts (e.g., _Saccharomyces cerevisiae_ and _Pichia pastoris_) and _Bacillus subtilis_ based on the endogenous phenyl donors supplied via either the mevalonate (MVA) pathway or the DXP pathway [35; 36; 37; 38].