KEGG   ORTHOLOGY: K20981
Entry
K20981            Tight     KO                                     
Symbol
LOVB
Name
lovastatin nonaketide synthase [EC:2.3.1.161]
Pathway
map00997  Biosynthesis of various other secondary metabolites
map01100  Metabolic pathways
map01110  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
   00997 Biosynthesis of various other secondary metabolites
    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                                     
Symbol
LOVC
Name
lovastatin enoyl reductase [EC:2.3.1.161]
Pathway
map00997  Biosynthesis of various other secondary metabolites
map01100  Metabolic pathways
map01110  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
   00997 Biosynthesis of various other secondary metabolites
    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
ec00997  Biosynthesis of various other secondary metabolites
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
rn00997  Biosynthesis of various other secondary metabolites
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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