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Literature summary extracted from

  • Lau, W.; Sattely, E.
    Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone (2015), Science, 349, 1224-1228.
    View publication on PubMedView publication on EuropePMC

Activating Compound

EC Number Activating Compound Comment Organism Structure
1.14.20.8 oxoglutarate dependent on Sinopodophyllum hexandrum

Application

EC Number Application Comment Organism
1.14.14.131 synthesis recombinant coexpression of the genes involved in the podophyllotoxin pathway permits to reconstitute the pathway to (-)-4'-demethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor, for production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin Sinopodophyllum hexandrum
1.14.14.132 synthesis recombinant coexpression of the genes involved in the podophyllotoxin pathway permits to reconstitute the pathway to (-)-4'-demethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor, for production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin Sinopodophyllum hexandrum
1.14.20.8 synthesis recombinant coexpression of the genes involved in the podophyllotoxin pathway permits to reconstitute the pathway to (-)-4'-demethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor, for production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin Sinopodophyllum hexandrum

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.14.14.131 gene Phex524 or CYP71CU1, expression analysis by qRT-PCR analysis, transcriptome mining to identify biosynthetic genes in the podophyllotoxin pathway, Agrobacterium-mediated functional transient expression in Nicotiana benthamiana Sinopodophyllum hexandrum
1.14.14.132 gene CYP82D61, expression analysis by qRT-PCR analysis, transcriptome mining to identify biosynthetic genes in the podophyllotoxin pathway, Agrobacterium-mediated functional transient expression in Nicotiana benthamiana Sinopodophyllum hexandrum
1.14.20.8 gene Phex30848 or 2-ODD, expression analysis by qRT-PCR analysis, transcriptome mining to identify biosynthetic genes in the podophyllotoxin pathway, Agrobacterium-mediated functional transient expression of the genes of the podophyllotoxin pathway in Nicotiana benthamiana Sinopodophyllum hexandrum
2.1.1.323 expressed in Nicotiana tabacum leaves and Escherichia coli Sinopodophyllum hexandrum

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.1.1.323 0.0014
-
 (-)-pluviatolide pH and temperature not specified in the publication Sinopodophyllum hexandrum

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.14.14.131 (-)-5'-demethoxyyatein + [reduced NADPH-hemoprotein reductase] + O2 Sinopodophyllum hexandrum
-
 (-)-5'-demethylyatein + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.20.8 (-)-yatein + 2-oxoglutarate + O2 Sinopodophyllum hexandrum
-
 (-)-deoxypodophyllotoxin + succinate + CO2 + H2O
-
 ?
2.1.1.323 S-adenosyl-L-methionine + (-)-pluviatolide Sinopodophyllum hexandrum
-
 S-adenosyl-L-homocysteine + (-)-bursehernin
-
 ?
2.1.1.330 S-adenosyl-L-methionine + (-)-5'-demethylyatein Sinopodophyllum hexandrum
-
 S-adenosyl-L-homocysteine + (-)-yatein
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.14.14.131 Sinopodophyllum hexandrum A0A0N9HTU1 or Sinopodophyllum hexandrum, gene Phex524 or CYP71CU1
-
1.14.14.132 Sinopodophyllum hexandrum A0A0N7F297 or Sinopodophyllum hexandrum, gene CYP82D61
-
1.14.20.8 Sinopodophyllum hexandrum A0A0N9HQ36 or Sinopodophyllum hexandrum, gene Phex30848 or 2-ODD
-
2.1.1.323 Sinopodophyllum hexandrum A0A0N9HMN6 mayapple
-
2.1.1.330 Sinopodophyllum hexandrum
-
 mayapple
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.14.14.131 (-)-5'-demethoxyyatein + [reduced NADPH-hemoprotein reductase] + O2
-
 Sinopodophyllum hexandrum (-)-5'-demethylyatein + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.14.132 (-)-4'-demethyl-deoxypodophyllotoxin + [reduced NADPH-hemoprotein reductase] + O2
-
 Sinopodophyllum hexandrum (-)-4'-demethylepipodophyllotoxin + [oxidized NADPH-hemoprotein reductase] + H2O
-
 ?
1.14.20.8 (-)-yatein + 2-oxoglutarate + O2
-
 Sinopodophyllum hexandrum (-)-deoxypodophyllotoxin + succinate + CO2 + H2O
-
 ?
2.1.1.323 additional information the enzyme cannot turn over (+)-pinoresinol Sinopodophyllum hexandrum ?
-
 ?
2.1.1.323 S-adenosyl-L-methionine + (-)-arctigenin low efficiency substrate Sinopodophyllum hexandrum S-adenosyl-L-homocysteine + ?
-
 ?
2.1.1.323 S-adenosyl-L-methionine + (-)-matairesinol low efficiency substrate Sinopodophyllum hexandrum S-adenosyl-L-homocysteine + ?
-
 ?
2.1.1.323 S-adenosyl-L-methionine + (-)-pluviatolide
-
 Sinopodophyllum hexandrum S-adenosyl-L-homocysteine + (-)-bursehernin
-
 ?
2.1.1.330 S-adenosyl-L-methionine + (-)-5'-demethylyatein
-
 Sinopodophyllum hexandrum S-adenosyl-L-homocysteine + (-)-yatein
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.14.20.8 deoxypodophyllotoxin synthase UniProt Sinopodophyllum hexandrum
2.1.1.323 OMT3
-
 Sinopodophyllum hexandrum
2.1.1.323 pluviatolide 4-O-methyltransferase
-
 Sinopodophyllum hexandrum
2.1.1.330 OMT1
-
 Sinopodophyllum hexandrum
2.1.1.330 Phex13114
-
 Sinopodophyllum hexandrum

Turnover Number [1/s]

EC Number Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
2.1.1.323 0.72
-
 (-)-pluviatolide pH and temperature not specified in the publication Sinopodophyllum hexandrum

Expression

EC Number Organism Comment Expression
1.14.20.8 Sinopodophyllum hexandrum the enzyme is induced by wounding of the mayapple leaves up
2.1.1.323 Sinopodophyllum hexandrum enzyme expression is strongly increased 9 h after leaf wounding up

General Information

EC Number General Information Comment Organism
1.14.14.131 metabolism the enzyme is involved in the biosynthesis of (-)-4'-demethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Biosynthetic pathway of (-)-podophyllotoxin, overview Sinopodophyllum hexandrum
1.14.14.132 metabolism the enzyme is involved in the biosynthesis of (-)-4'-demethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Biosynthetic pathway of (-)-podophyllotoxin, overview Sinopodophyllum hexandrum
1.14.20.8 metabolism the oxoglutarate-dependent dioxygenase is involved in the biosynthesis of (-)-4'-demethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Biosynthetic pathway of (-)-podophyllotoxin, overview Sinopodophyllum hexandrum