Protein: Lovastatin nonaketide synthase, enoyl reductase component lovC (EC 2.3.1.161) (Lovastatin biosynthesis cluster protein C) (Trans-enoyl reductase lovC) (Q0C8M1)
Organism: Aspergillus terreus (strain NIH 2624 / FGSC A1156)
Function: Trans-enoyl reductase; part of the gene cluster that mediates the biosynthesis of lovastatin (also known as mevinolin, mevacor or monacolin K), a hypolipidemic inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR). The first step in the biosynthesis of lovastatin is the production of dihydromonacolin L acid by the lovastatin nonaketide synthase lovB and the trans-acting enoyl reductase lovC via condensation of one acetyl-CoA unit and 8 malonyl-CoA units. Dihydromonacolin L acid is released from lovB by the thioesterase lovG. Next, dihydromonacolin L acid is oxidized by the dihydromonacolin L monooxygenase lovA twice to form monacolin J acid. The 2-methylbutyrate moiety of lovastatin is synthesized by the lovastatin diketide synthase lovF via condensation of one acetyl-CoA unit and one malonyl-CoA unit. Finally, the covalent attachment of this moiety to monacolin J acid is catalyzed by the transesterase lovD to yield lovastatin. LovD has broad substrate specificity and can also convert monacolin J to simvastatin using alpha-dimethylbutanoyl-S-methyl-3-mercaptopropionate (DMB-S-MMP) as the thioester acyl donor, and can also catalyze the reverse reaction and function as hydrolase in vitro. LovD has much higher activity with LovF-bound 2-methylbutanoate than with free diketide substrates.
InterPro domains:
- IPR036291: NAD(P)-binding domain superfamily (homologous_superfamily) [125-275]
- IPR020843: Enoylreductase domain (domain) [19-358]
- IPR011032: GroES-like superfamily (homologous_superfamily) [9-145]
- IPR047122: Trans-enoyl reductase-like (family) [10-361]
- IPR013154: Alcohol dehydrogenase-like, N-terminal (domain) [36-122]
Sequence:
MGDQPFIPPPQQTALTVNDHDEVTVWNAAPCPILPRDQVYVRVEAVAINPSDTKMRGQFATPWAFLGTDYAGTVVAVGSDVTHIQVGDRVYGAQNEMCPRTPDQGAFSQYTVTRGRVWAKIPKGLSFEQAAALPAGISTAGLAMKLLGLPLPSPSADQPPAHSKPVYVLVYGGSTATATVTMQMLRLSGYIPIATCSPHNFDLAKSRGAEEVFDYRAPNLAQTIRTYTKNNLRYSLDCITNVESTTFCFAAIGRAGGHYVSLNPFPEHAATRKMVTTDWTLGPTIFGEGSTWPAPYGRPGSEEERQFGEDLWRIAGQLVEDGRLAHHPLRVVQGGFDQIKQGMELVRKGELSGEKLVVRLEGP
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0036094 (small molecule binding), GO:0043167 (ion binding), GO:0097159 (organic cyclic compound binding), GO:1901363 (heterocyclic compound binding), GO:0016491 (oxidoreductase activity), GO:0043168 (anion binding), GO:0000166 (nucleotide binding), GO:1901265 (nucleoside phosphate binding), GO:0070402 (NADPH binding), GO:0017076 (purine nucleotide binding), GO:0030554 (adenyl nucleotide binding), GO:0050661 (NADP binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:0044249 (cellular biosynthetic process), GO:0009404 (toxin metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006629 (lipid metabolic process), GO:0046483 (heterocycle metabolic process), GO:0030638 (polyketide metabolic process), GO:1901334 (lactone metabolic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009403 (toxin biosynthetic process), GO:1901568 (fatty acid derivative metabolic process), GO:0008610 (lipid biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0030639 (polyketide biosynthetic process), GO:0043386 (mycotoxin biosynthetic process), GO:1901570 (fatty acid derivative biosynthetic process), GO:1901336 (lactone biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex)