The Enzyme Database

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Accepted name: lovastatin nonaketide synthase
Reaction: 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
For diagram of polyketides biosynthesis, click here
Glossary: dihydromonacolin L acid = (3R,5R)-7-[(1S,2S,4aR,6R,8aS)-2,6-dimethyl-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate
Other name(s): LNKS; LovB; LovC; acyl-CoA:malonyl-CoA C-acyltransferase (decarboxylating, oxoacyl- and enoyl-reducing, thioester-hydrolysing)
Systematic name: acyl-CoA:malonyl-CoA C-acyltransferase (dihydromonacolin L acid-forming)
Comments: 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, 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.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number: 235426-97-8
1.  Ma, S.M., Li, J.W., Choi, J.W., Zhou, H., Lee, K.K., Moorthie, V.A., Xie, X., Kealey, J.T., Da Silva, N.A., Vederas, J.C. and Tang, Y. Complete reconstitution of a highly reducing iterative polyketide synthase. Science 326 (2009) 589–592. [DOI] [PMID: 19900898]
2.  Kennedy, J., Auclair, K., Kendrew, S.G., Park, C., Vederas, J.C. and Hutchinson, C.R. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284 (1999) 1368–1372. [DOI] [PMID: 10334994]
3.  Auclair, K., Sutherland, A., Kennedy, J., Witter, D.J., van der Heever, J.P., Hutchinson, C.R. and Vederas, J.C. Lovastatin nonaketide synthase catalyses an intramolecular Diels-Alder reaction of a substrate analogue. J. Am. Chem. Soc. 122 (2000) 11519–11520.
[EC created 2002, modified 2015, modified 2016, modified 2019]

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