Literature summary for 4.2.3.17 extracted from

Engels, B.; Dahm, P.; Jennewein, S.
Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards Taxol (Paclitaxel) production (2008), Metab. Eng., 10, 201-206.

Activating Compound

Activating Compound	Comment	Organism	Structure
additional information	coexpression of geranylgeranyl diphosphate synthase gene from Sulfolobus acidocaldarius and codon optimzing of the Taxus chinensis taxadiene synthase gene increases the production of taxadiene in Saccharomyces cerevisiae	Taxus chinensis

Application

Application	Comment	Organism
drug development	cancer therapy, taxadiene is the precursor of paclitaxel, a chemotherapeutic agents	Taxus chinensis

Cloned(Commentary)

Cloned (Comment)	Organism
Expression of Taxus chinensis taxadiene synthase (expression of a transgene encoding the pseudomature form which lacks the N-terminal 74-amino acid residue plastid-targeting sequence) in Saccharomyces cerevisiae alone does not increase taxadiene levels because of insufficient levels of the universal diterpenoid precursor geranylgeranyl diphosphate. Coexpression of Taxus chinensis taxadiene synthase and geranylgeranyl diphosphate synthase fails to increase levels. Replacement the Taxus chinensis geranylgeranyl diphosphate synthase with its counterpart from Sulfolobus acidocaldarius, which does not compete with steroid synthesis, and codon optimized the Taxus chinensis taxadiene synthase gene to ensure high-level expression, resulting in a increase in taxadiene as well as significant amounts of geranylgeraniol, suggesting taxadiene levels can be increased even further.	Taxus chinensis

Cloned (Comment)

Organism

Expression of Taxus chinensis taxadiene synthase (expression of a transgene encoding the pseudomature form which lacks the N-terminal 74-amino acid residue plastid-targeting sequence) in Saccharomyces cerevisiae alone does not increase taxadiene levels because of insufficient levels of the universal diterpenoid precursor geranylgeranyl diphosphate. Coexpression of Taxus chinensis taxadiene synthase and geranylgeranyl diphosphate synthase fails to increase levels. Replacement the Taxus chinensis geranylgeranyl diphosphate synthase with its counterpart from Sulfolobus acidocaldarius, which does not compete with steroid synthesis, and codon optimized the Taxus chinensis taxadiene synthase gene to ensure high-level expression, resulting in a increase in taxadiene as well as significant amounts of geranylgeraniol, suggesting taxadiene levels can be increased even further.

Taxus chinensis

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
geranylgeranyl diphosphate	Taxus chinensis	taxadiene biosynthetic pathway	taxa-4(5),11(12)-diene + diphosphate	precursor of the chemotherapeutic agent taxol	ir

Organism

Organism	UniProt	Comment	Textmining
Taxus chinensis	-	production of enzyme in Saccharomyces cerevisiae	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
cell culture	-	Taxus chinensis	-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
additional information	-	Replacement of the geranylgeranyl diphosphate synthase with the enzyme from Sulfolobus acidocaldarius and codon optimizing of the Taxus chinensis taxadiene synthase gene to ensure high-level expression, resulting in a 40fold increase in taxadiene to 8.770.85 mg/l as well as significant amounts of geranylgeraniol (33.1 mg/l)	Taxus chinensis

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
geranylgeranyl diphosphate	taxadiene biosynthetic pathway	Taxus chinensis	taxa-4(5),11(12)-diene + diphosphate	precursor of the chemotherapeutic agent taxol	ir

Synonyms

Synonyms	Comment	Organism
taxadiene synthase	-	Taxus chinensis