KEGG   ORTHOLOGY: K20981
Entry
K20981            Tight     KO                                     

Name
LOVB
Definition
lovastatin nonaketide synthase [EC:2.3.1.161]
Pathway
ko00999  Biosynthesis of various secondary metabolites - part 1
ko01100  Metabolic pathways
ko01110  Biosynthesis of secondary metabolites
Module
M00893  Lovastatin biosynthesis, malonyl-CoA => lovastatin acid
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09110 Biosynthesis of other secondary metabolites
   00999 Biosynthesis of various secondary metabolites - part 1
    K20981  LOVB; lovastatin nonaketide synthase
Enzymes [BR:ko01000]
 2. Transferases
  2.3  Acyltransferases
   2.3.1  Transferring groups other than aminoacyl groups
    2.3.1.161  lovastatin nonaketide synthase
     K20981  LOVB; lovastatin nonaketide synthase
Other DBs
RN: R07251
GO: 0050637
Genes
AG: AAD39830(LOVB)
Reference
  Authors
Ma SM, Li JW, Choi JW, Zhou H, Lee KK, Moorthie VA, Xie X, Kealey JT, Da Silva NA, Vederas JC, Tang Y
  Title
Complete reconstitution of a highly reducing iterative polyketide synthase.
  Journal
Science 326:589-92 (2009)
DOI:10.1126/science.1175602
  Sequence

KEGG   ORTHOLOGY: K20982
Entry
K20982            Tight     KO                                     

Name
LOVC
Definition
lovastatin enoyl reductase [EC:2.3.1.161]
Pathway
ko00999  Biosynthesis of various secondary metabolites - part 1
ko01100  Metabolic pathways
ko01110  Biosynthesis of secondary metabolites
Module
M00893  Lovastatin biosynthesis, malonyl-CoA => lovastatin acid
Brite
KEGG Orthology (KO) [BR:ko00001]
 09100 Metabolism
  09110 Biosynthesis of other secondary metabolites
   00999 Biosynthesis of various secondary metabolites - part 1
    K20982  LOVC; lovastatin enoyl reductase
Enzymes [BR:ko01000]
 2. Transferases
  2.3  Acyltransferases
   2.3.1  Transferring groups other than aminoacyl groups
    2.3.1.161  lovastatin nonaketide synthase
     K20982  LOVC; lovastatin enoyl reductase
Other DBs
RN: R07251
COG: COG0604
Genes
AG: AAD34554(LOVC)
Reference
  Authors
Ma SM, Li JW, Choi JW, Zhou H, Lee KK, Moorthie VA, Xie X, Kealey JT, Da Silva NA, Vederas JC, Tang Y
  Title
Complete reconstitution of a highly reducing iterative polyketide synthase.
  Journal
Science 326:589-92 (2009)
DOI:10.1126/science.1175602
  Sequence

KEGG   ENZYME: 2.3.1.161
Entry
EC 2.3.1.161                Enzyme                                 

Name
lovastatin nonaketide synthase;
LNKS;
LovB;
LovC;
acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing, thioester-hydrolysing)
Class
Transferases;
Acyltransferases;
Transferring groups other than aminoacyl groups
Sysname
acyl-CoA:malonyl-CoA C-acyltransferase (dihydromonacolin L acid-forming)
Reaction(IUBMB)
9 malonyl-CoA + 11 NADPH + 10 H+ + S-adenosyl-L-methionine + holo-[lovastatin nonaketide synthase] = dihydromonacolin L-[lovastatin nonaketide synthase] + 9 CoA + 9 CO2 + 11 NADP+ + S-adenosyl-L-homocysteine + 6 H2O [RN:R07251]
Reaction(KEGG)
R07251
Substrate
malonyl-CoA [CPD:C00083];
NADPH [CPD:C00005];
H+ [CPD:C00080];
S-adenosyl-L-methionine [CPD:C00019];
holo-[lovastatin nonaketide synthase]
Product
dihydromonacolin L-[lovastatin nonaketide synthase];
CoA [CPD:C00010];
CO2 [CPD:C00011];
NADP+ [CPD:C00006];
S-adenosyl-L-homocysteine [CPD:C00021];
H2O [CPD:C00001]
Comment
This fungal enzyme system comprises a multi-functional polyketide synthase (PKS) and an enoyl reductase. The PKS catalyses many of the chain building reactions of EC 2.3.1.85, fatty-acid synthase system, as well as a reductive methylation and a Diels-Alder reaction, while the reductase is responsible for three enoyl reductions that are necessary for dihydromonacolin L acid production.
History
EC 2.3.1.161 created 2002, modified 2015, modified 2016, modified 2019
Pathway
ec00999  Biosynthesis of various secondary metabolites - part 1
ec01100  Metabolic pathways
ec01110  Biosynthesis of secondary metabolites
Orthology
K20981  lovastatin nonaketide synthase
K20982  lovastatin enoyl reductase
Reference
1  [PMID:19900898]
  Authors
Ma SM, Li JW, Choi JW, Zhou H, Lee KK, Moorthie VA, Xie X, Kealey JT, Da Silva NA, Vederas JC, Tang Y
  Title
Complete reconstitution of a highly reducing iterative polyketide synthase.
  Journal
Science 326:589-92 (2009)
DOI:10.1126/science.1175602
  Sequence
Reference
2  [PMID:10334994]
  Authors
Kennedy J, Auclair K, Kendrew SG, Park C, Vederas JC, Hutchinson CR.
  Title
Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis.
  Journal
Science 284:1368-72 (1999)
DOI:10.1126/science.284.5418.1368
  Sequence
Reference
3
  Authors
Auclair, K., Sutherland, A., Kennedy, J., Witter, D.J., van der Heever, J.P., Hutchinson, C.R. and Vederas, J.C.
  Title
Lovastatin nonaketide synthase catalyses an intramolecular Diels-Alder reaction of a substrate analogue.
  Journal
J Am Chem Soc 122:11519-11520 (2000)
Other DBs
ExplorEnz - The Enzyme Database: 2.3.1.161
IUBMB Enzyme Nomenclature: 2.3.1.161
ExPASy - ENZYME nomenclature database: 2.3.1.161
BRENDA, the Enzyme Database: 2.3.1.161
CAS: 235426-97-8

KEGG   REACTION: R07251
Entry
R07251                      Reaction                               

Name
acyl-CoA:malonyl-CoA C-acyltransferase (dihydromonacolin L-[acp]-forming)
Definition
9 Malonyl-CoA + 11 NADPH + 10 H+ + S-Adenosyl-L-methionine + Acyl-carrier protein <=> Dihydromonacolin L-[acyl-carrier protein] + 9 CoA + 9 CO2 + 11 NADP+ + S-Adenosyl-L-homocysteine + 6 H2O
Equation
9 C00083 + 11 C00005 + 10 C00080 + C00019 + C00229 <=> C21108 + 9 C00010 + 9 C00011 + 11 C00006 + C00021 + 6 C00001
Comment
multi-step reaction
Acy-carrier protein is acp domain of LOVB [KO:K20981].
Reaction class
RC00003  C00019_C00021
RC00004  C00010_C00083
RC00039  C00229_C21108
Enzyme
Pathway
rn00999  Biosynthesis of various secondary metabolites - part 1
rn01100  Metabolic pathways
rn01110  Biosynthesis of secondary metabolites
Module
M00893  Lovastatin biosynthesis, malonyl-CoA => lovastatin acid
Orthology
K20981  lovastatin nonaketide synthase [EC:2.3.1.161]
K20982  lovastatin enoyl reductase [EC:2.3.1.161]
Other DBs
RHEA: 18568

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