## 1 Introduction  
A monocyclic sesquiterpene alcohol, (\(-\))-\(\alpha\)-bisabolol, has been used in pharmaceuticals and cosmetics as it displays the beneficial effects of skin healing and anti-inflammation [1; 2; 3; 4; 5]. The global market of (\(-\))-\(\alpha\)-bisabolol is expected to reach $73 million by 2020, with an annual growth rate of 5.9% from 2016 [6]. Commercially available (\(-\))-\(\alpha\)-bisabolol is currently produced by the steam-distillation method using oils extracted from German chamomile or Brazilian candeia tree [7; 8]. This process, however, has caused environmental issues, as well as economic concerns owing to a low extraction yield [8]. Natural (\(-\))-\(\alpha\)-bisabolol was obtained from the candeia tree with a yield of approximately 0.018 g/g\({}_{\mathsf{canteia}\,\mathrm{power}}\) through CO\({}_{2}\) supercritical extraction at 40 \({}^{\circ}\)C and 10 MPa [8]. Although a chemical process has been developed to produce (\(-\))-\(\alpha\)-bisabolol, it forms diastereomers of (\(-\))-\(\alpha\)-bisabolol ((+)-\(\alpha\)-bisabolol and (\(\pm\))-epi-\(\alpha\)-bisabolol), and thus requires auxiliary purification steps [9]. In this context, the biological production of naturally occurring (\(-\))-\(\alpha\)-bisabolol using engineered microbes may be an attractive alternative to the current production processes of (\(-\))-\(\alpha\)-bisabolol. (\(-\))-\(\alpha\)-Bisabolol can be synthesized from five-carbon building blocks of isopentenyl diphosphate (IPP) and its isomer dimethyl allypyrophosphate (DMAPP) (Figure 1) [10]. Both universal precursors of terpenoids can be produced from the MVA or the 2-C-methyl-D-erythnitol 4-phosphate (MEP) pathway. Exogenous MVA or endogenous MEP pathway has been employed in engineered _E. coli_ for production of various terpenoids. Although the MEP pathway exhibits higher theoretical yield than the MVA pathway, the exogenous MVA pathway showed generally higher production than the endogenous MEP pathway [11]. In particular, the MVA pathway has been harnessed to efficiently convert acetyl-CoA to several terpenoids including (\(-\))-\(\alpha\)-bisabolol [12]. Both universal isoprene units, IPP and DMAPP are converted into farnesyl pyrophosphate (FPP), which is catalyzed by FPP synthase encoded by the endogenous _ispA_ gene, which is then used for production of (\(-\))-\(\alpha\)-bisabolol by the (\(-\))-\(\alpha\)-bisabolol synthase (BBS, Figure 1). Figure 1: Biosynthetic pathway of (\(-\))-\(\alpha\)-bisabolol in engineered _E. coli_. The endogenous MEP) pathway consists of DXS (deoxyxyylulose-5-phosphate synthase), DXR (deoxyxyylulose 5-phosphate reductio isomerase), CMS (2-C-methylerythnitol 4-phosphate cytidyl transferase), CMK (4-(cytidine 5’-diphospho)-2-C-methylerythnitol kinase), MDS (2-C-methylerythnitol 2,4-cyclodiphosphate synthase), HDS ((E)-4-hydroxy-3-methylbut-2-enyl diphosphate reductase), and HDR (hydroxymethylbutenyl  
diphosphate reductase). The MEP pathway begins with the condensation of G-3-P (glyceraldehyde reductase 3-phosphate) and pyruvate that is converted from G-3-P by endogenous nicotinamide adenine dinucleotide (NAD\({}^{+}\))-dependent GAPDH (glyceraldehyde-3-phosphate dehydrogenase) coded by _gapA_ and nicotinamide adenine dinucleotide phosphate (NADP\({}^{+}\))-dependent GAPDH coded by _gapC_ from _Clostidium acetobutylticum_ (_C. acetobutylcium_). The exogenous MVA pathway consists of MvaE (dual function of acetoacetyl-CoA thiolose and 3-hydroxy-3-methylglutural-CoA reductase), MvaS (3-hydroxy-3-methylglutural-CoA synthase), MvaK1 (MVA kinase), MvaK2 (phosphomevalonate kinase), MvaD (mevalonate 5-pyrophosphate decarboxylase), Idi (isopentenyl diphosphate isomerase), IspA (geranyl diphosphate synthase or FPP synthase), and _Mr_BBS ((-)-\(\alpha\)-bisabolol synthase of _Matricaria recuitita_). Endogenous and exogenous genes are depicted in brown and green, respectively. The biological production of (\(-\))-\(\alpha\)-bisabolol has been explored using well-studied microbes such as _Saccharomyces cerevisiae_ (_S.