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Review
. 2022 Aug 2;21(1):152.
doi: 10.1186/s12934-022-01865-7.

Advances in biosynthesis of scopoletin

Bo-Tao He  1 , Zhi-Hua Liu  1 , Bing-Zhi Li  2 , Ying-Jin Yuan  1
Affiliations
Review

Advances in biosynthesis of scopoletin

Bo-Tao He et al. Microb Cell Fact. .

Abstract

Scopoletin is a typical example of coumarins, which can be produced in plants. Scopoletin acts as a precursor for pharmaceutical and health care products, and also possesses promising biological properties, including antibacterial, anti-tubercular, anti-hypertensive, anti-inflammatory, anti-diabetic, and anti-hyperuricemic activity. Despite the potential benefits, the production of scopoletin using traditional extraction processes from plants is unsatisfactory. In recent years, synthetic biology has developed rapidly and enabled the effective construction of microbial cell factories for production of high value-added chemicals. Herein, this review summarizes the progress of scopoletin biosynthesis in artificial microbial cell factories. The two main pathways of scopoletin biosynthesis are summarized firstly. Then, synthetic microbial cell factories are reviewed as an attractive improvement strategy for biosynthesis. Emerging techniques in synthetic biology and metabolic engineering are introduced as innovative tools for the efficient synthesis of scopoletin. This review showcases the potential of biosynthesis of scopoletin in artificial microbial cell factories.

Keywords: Biosynthesis; Coumarins; Microbial cell factory; Scopoletin; Synthetic biology.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The plant sources and pharmaceutical values of scopoletin
Fig. 2
Fig. 2
Biosynthetic pathway of scopoletin from glucose or lignin-derived aromatics. The compounds in the purple box are the two major monomers derived from lignin after pretreatment. The compound in the orange box is scopoletin, which is the target product produced by the microbial cell factory in this paper. TAL: tyrosine ammonia lyase; PAL: phenylalanine ammonia lyase; 4CL: 4-coumarate CoA ligase; FCS: feruloyl-CoA synthase; C4H: cinnamate-4-hydroxylase; HHA: 4-hydroxyphenylacetic acid 3-hydroxylase A; C3H: coumarate-3-hydroxylase; F6’H: feruloyl-CoA 6'-hydroxylase; C2'H: coumaroyl CoA 2'-hydroxylase; COSY: coumarin synthase; S8H: scopoletin 8-hydroxylase; CCoAOMT: caffeoyl-CoA O-methyltransferase; CYP82C4: cytochrome P450 family B2 subfamily C polypeptide 4 enzyme. Three consecutive arrows indicate multiple biosynthetic steps
Fig. 3
Fig. 3
Synthetic biology methods for biosynthetic regulation to increase the titer, rate, and yield (TRY) of product. A Diagram of artificial neural network-guided biosynthetic regulation. B Pathway optimization based on the promoter library containing different expression intensities. C Novel enzyme search and initial enzyme modification, optimization and protein design. C1, compound 1; C2, compound 2; C3, compound 3; C4, compound 4; E1, enzyme 1; E2, enzyme 2; E3, enzyme 3. D The process for transforming exogenous genes and exogenous pathways into engineered strains by means of plasmid construction or genomic integration. E The engineering process reduces biomass, reduces the loss of carbon sources in branching pathways, reduces metabolic competition between desired products and byproducts, and ensures the continued accumulation of the desired products
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