2.3.1.161: lovastatin nonaketide synthase
This is an abbreviated version!
For detailed information about lovastatin nonaketide synthase, go to the full flat file.
Word Map on EC 2.3.1.161
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2.3.1.161
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polyketide
-
iterative
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synthases
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terreus
-
medicine
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enoyl
-
megasynthase
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cholesterol-lowering
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s-adenosylmethionine
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diketide
-
2-methylbutyrate
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pyrones
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transesterase
- 2.3.1.161
- polyketide
-
iterative
- synthases
- terreus
- medicine
-
enoyl
-
megasynthase
-
cholesterol-lowering
- s-adenosylmethionine
-
diketide
- 2-methylbutyrate
- pyrones
-
transesterase
Reaction
9 malonyl-CoA
+
11 NADPH
+
10 H+
+
Synonyms
LNKS, lovastatin nonaketide synthase, LovB, synthase, lovastatin nonaketide
ECTree
2.3.1.161 lovastatin nonaketide synthaseAdvanced search results
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results (Substrates Products
Substrates Products on EC 2.3.1.161 - lovastatin nonaketide synthase
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SUBSTRATE 
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(4E,6E)-2-methyl-3-oxoocta-4,6-dienoyl-S-ACP + NADPH + H+
(4E,6E)-2-methyl-3-hydroxyocta-4,6-dienoyl-S-ACP + NADP+
reaction of ketoreductase subunit, natural substrate. ACP = acyl-carrier protein
-
-
?
(4E,6E)-3-oxoocta-4,6-dienoyl-N-acetylcysteamine + S-adenosyl-L-methionine
(4E,6E)-2-methyl-3-oxoocta-4,6-dienoyl-N-acetylcysteamine + S-adenosyl-L-homocysteine
reaction of methyltransferase subunit, natural substrate analogue. ACP = acyl-carrier protein
-
-
?
(4E,6E)-3-oxoocta-4,6-dienoyl-S-ACP + S-adenosyl-L-methionine
(4E,6E)-2-methyl-3-oxoocta-4,6-dienoyl-S-ACP + S-adenosyl-L-homocysteine
reaction of methyltransferase subunit, natural substrate. ACP = acyl-carrier protein
-
-
?
2-methyl-3-oxohexanoyl-N-acetylcysteamine + NADPH + H+
3-hydroxy-2-methylhexanoyl-N-acetylcysteamine + NADP+
reaction of ketoreductase subunit, natural substrate
-
-
?
3-oxohexanoyl-N-acetylcysteamine + NADPH + H+
3-hydroxyhexanoyl-N-acetylcysteamine + NADP+
reaction of ketoreductase subunit, natural substrate
-
-
?
3-oxooctanoyl-N-acetylcysteamine + S-adenosyl-L-methionine
2-methyl-3-oxooctanoyl-N-acetylcysteamine + S-adenosyl-L-homocysteine
reaction of methyltransferase subunit, artificial substrate. 0.3% of the activity with (4E,6E)-3-oxoocta-4,6-dienoyl-N-acetylcysteamine
-
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
acetyl-CoA + malonyl-CoA + NADPH + H+ + S-adenosyl-L-methionine
4-hydroxy-6-[(1E,3E,5E)-1-methylhepta-1,3,5-trien-1-yl]-2H-pyran-2-one + 4-hydroxy-6-[(1E,3E,5E,7E)-3-methylnona-1,3,5,7-tetraen-1-yl]-2H-pyran-2-one + CoA + CO2 + NADP+ + S-adenosyl-L-homocysteine + H2O
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in absence of accessory protein LovC, formation of truncated pyrones 4-hydroxy-6-[(1E,3E,5E)-1-methylhepta-1,3,5-trien-1-yl]-2H-pyran-2-one + 4-hydroxy-6-[(1E,3E,5E,7E)-3-methylnona-1,3,5,7-tetraen-1-yl]-2H-pyran-2-one. Chemical synthesis of these truncated pyrones for analysis of enzyme reaction
-
?
acetyl-CoA + malonyl-CoA + NADPH + H+ + S-adenosyl-L-methionine
?
in the absence of the accessory protein LovC, LovB forms conjugated pyrones as truncated polyketide synthase products
-
-
?
acetyl-CoA + malonyl-CoA + NADPH + H+ + S-adenosyl-L-methionine
dihydromonacolin L + CoA + CO2 + NADP+ + S-adenosyl-L-homocysteine + H2O
additional information
?
-
the methyltransferase domain displays methylation activity toward different beta-ketoacyl groups, it is exceptionally selective toward its naturally programmed beta-keto-dienyltetraketide substrate with respect to both chain length and functionalization. The ketoreductase domain displays broader substrate specificity toward different beta-ketoacyl groups
-
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
-
reaction mechanism
-
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
-
enzyme contains six active sites: ketosynthase, acyltransferase, dehydratase, enoyl reductase, ketoreductase and acyl carrier protein
-
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
-
enzyme contains six active sites: ketosynthase, acyltransferase, dehydratase, enoyl reductase, ketoreductase and acyl carrier protein
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
-
enzyme also displays Diels-Alderase activity in vitro
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
-
enzyme also displays Diels-Alderase activity in vitro
-
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
-
reaction mechanism, interaction with LovC
-
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
-
reaction mechanism, enzyme interacts with LovC to catalyze 35 separate reactions in the biosynthesis of dihydrononacolin
-
-
?
acetyl-CoA + 8 malonyl-CoA + 11 NADPH + S-adenosyl-L-methionine + 11 H+
dihydromonacolin L + 9 CoA + 8 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O
-
accessory protein LovC is needed: Loading of the megasynthase by malonyl-CoA is presumably followed by decarboxylation to yield the acetyl starter unit. Each round of Claisen condensation is catalyzed by the KS domain, whereas the growing polyketide is tethered to the phosphopantetheinyl arm of the ACP. After each condensation, the polyketide is subjected to a different combination of tailoring, which can include alpha-methylation by the MT domain, beta-ketoreduction by the KR domain, beta-dehydration by the DH domain, and alpha-beta-enoylreduction by the dissociated LovC. The different tailoring permutations after each round of chain extension yield a triene-containing hexaketide thioester that can undergo a stereospecific Diels-Alder cyclization to yield the decalin portion. After formation of the nonaketide, the chain is released to yield the ring-open form. In the absence of LovC, methylated hexa- and heptaketide pyrones are the primary products.
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-
ir
acetyl-CoA + malonyl-CoA + NADPH + H+ + S-adenosyl-L-methionine
dihydromonacolin L + CoA + CO2 + NADP+ + S-adenosyl-L-homocysteine + H2O
-
-
-
?
acetyl-CoA + malonyl-CoA + NADPH + H+ + S-adenosyl-L-methionine
dihydromonacolin L + CoA + CO2 + NADP+ + S-adenosyl-L-homocysteine + H2O
-
in presence of accessory protein LovC, formation of dihydrononacolin C
-
?
acetyl-CoA + malonyl-CoA + NADPH + H+ + S-adenosyl-L-methionine
dihydromonacolin L + CoA + CO2 + NADP+ + S-adenosyl-L-homocysteine + H2O
-
reaction catalyzed by Lov B + Loc C. Mutant disruoted at the lovC gene lacks the ability to produce dihydrononacolin L
-
-
?
acetyl-CoA + malonyl-CoA + NADPH + H+ + S-adenosyl-L-methionine
dihydromonacolin L + CoA + CO2 + NADP+ + S-adenosyl-L-homocysteine + H2O
in the presence of the accessory protein LovC
-
-
?
