Literature summary for 4.2.3.24 extracted from

Jiang-Qiang, K.; Wei, W.; Li-Na, W.; Xiao-Dong, Z.; Ke-Di, C.; Ping, Z.
The improvement of amorpha-4,11-diene production by a yeast-conform variant (2009), J. Appl. Microbiol., 106, 941-951.

Application

Application	Comment	Organism
drug development	amorpha-4,11-diene is a precursor of artemisinin, an endoperoxide sesquiterpene lactone produced in plant Artemisia annua L., one of the most important agents in the treatment of malaria, particularly in the form of artemisinin-based combination therapies	Artemisia annua

Cloned(Commentary)

Cloned (Comment)	Organism
The ADS gene is mutated to the yeast-conform variant ADSm (based on the original DNA sequence of the wild-type gene, the plant gene codons are modified to Saccharomyces cerevisiae preferred with the intact protein primary structure, production in a transformed yeast.) The 8 low-usage codons, AGG (Arg), CGA (Arg), CGG (Arg), CGC (Arg), CCG (Pro), CTC (Leu), GCG (Ala) and ACG (Thr) in ADSm gene are changed with bias codons in Saccharomyces cerevisiae. The synonymous codons of 5 amino acids are changed into one preferred codon in ADSm gene, such as Gln (CAA), Glu (GAA), Cys (TGT), Arg (AGA) and Gly (GGT), which can improve the abundance of cognate tRNA when translated. Three genes, encoding the FPP synthase, HMG-CoA reductase and ADS, are plasmid-transformed together.	Artemisia annua

Cloned (Comment)

Organism

The ADS gene is mutated to the yeast-conform variant ADSm (based on the original DNA sequence of the wild-type gene, the plant gene codons are modified to Saccharomyces cerevisiae preferred with the intact protein primary structure, production in a transformed yeast.) The 8 low-usage codons, AGG (Arg), CGA (Arg), CGG (Arg), CGC (Arg), CCG (Pro), CTC (Leu), GCG (Ala) and ACG (Thr) in ADSm gene are changed with bias codons in Saccharomyces cerevisiae. The synonymous codons of 5 amino acids are changed into one preferred codon in ADSm gene, such as Gln (CAA), Glu (GAA), Cys (TGT), Arg (AGA) and Gly (GGT), which can improve the abundance of cognate tRNA when translated. Three genes, encoding the FPP synthase, HMG-CoA reductase and ADS, are plasmid-transformed together.

Artemisia annua

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
2-trans,6-trans-farnesyl diphosphate	Artemisia annua	-	amorpha-4,11-diene + diphosphate	amorpha-4,11-diene is a precursor of artemisin, a three-step oxidation is necessary	?

Organism

Organism	UniProt	Comment	Textmining
Artemisia annua	Q9AR04	sequence of wild-type enzyme; yeast-conform variant of the gene, production in a transformed yeast	-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
additional information	-	Strains transformed with the yeast-conform allele (ADSm) are more efficient in terms of production of amorpha-4,11-diene than those transformed with the plant gene. Production of amorpha-4,11-diene in the engineered yeasts containing ADSm gene is 10-20fold higher than the control	Artemisia annua

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
2-trans,6-trans-farnesyl diphosphate	-	Artemisia annua	amorpha-4,11-diene + diphosphate	amorpha-4,11-diene is a precursor of artemisin, a three-step oxidation is necessary	?

Synonyms

Synonyms	Comment	Organism
ADS	-	Artemisia annua
amorpha-4,11-diene synthase	-	Artemisia annua