Overview of production of plant diterpenoids in different hosts.
Host | Diterpene | Metabolic engineering strategies | Titer (mg/l) | Reference |
---|---|---|---|---|
◆ Screening of optimal GGPPS and ◆ Overexpression of three key enzymes in MEP pathway ◆ Culturing strain in a bioreactor |
578 | [114] | ||
Steviol | ◆ Optimization of the upstream pathway ◆ Screening of proper ◆ Truncating the N terminus-modified mutants of kaurene oxidase and attachment of soluble tags ◆ Codon optimization and increasing the copy number of ◆ Introduction of cytochrome b5 (CYB5) ◆ Site-directed mutation of |
1073.8 | [115] | |
Taxadiene | ◆ Modularization of the taxadiene metabolic pathway ◆ Using systematic multivariate analysis to achieve a balance of the two modules |
1020 | [9] | |
Miltiradiene | ◆ Overexpression of the pathway genes ◆ Downregulation of ◆ Knocked out transcriptional regulators ◆ Optimization of the medium ◆ Fusion of ◆ Protein modification of |
3500 | [117] | |
Forskolin | ◆ Fusion of ◆ Overexpression of ◆ Truncating the N terminus of ◆ Fusion of ◆ Regulation of copy numbers of the target genes, amplification of the endoplasmic reticulum (ER) area and cofactor metabolism enhancement ◆ Fed-batch fermentation |
21.47 | [119] | |
Carnosic acid | ◆ Overexpression of ◆ Codon-optimization, N-terminus truncation, and fusion of ◆ Used ◆ Co-expression of ◆ Overexpression of ◆ Overexpression of ◆ Batch and fed-batch fermentation |
24.65 | [120] | |
Rubusoside | ◆ KS from ◆ Overexpression of ◆ Site-directed mutation of ◆ Replacing promoter of ◆ Overexpression of the efflux-pump ◆ Knocking out |
1368.6 | [94] | |
Gibberellin | ◆ Downregulating the endogenous squalene synthase gene ◆ Choosing ◆ Codon-optimization of all genes ◆ Gene ◆ N-terminus truncation of |
GA4 17.29 GA3 2.93 |
[38] | |
Sclareol | ◆ Codon optimization of terpene synthase ◆ All transgenes were driven by the PSAD promoter and FDX1 terminator ◆ Using GGPPS from |
656 | [121] |