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

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