Protein: Dihydromonacolin L-[lovastatin nonaketide synthase] thioesterase (Q9Y7C9)
Organism: Aspergillus terreus
Function: Esterase; 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
Sequence: MRYQASPALVKAPRALLCIHGAGCSPAIFRVQLSKLRAALRENFEFVYVTAPFPSSAGPGILPVFADLGPYYSWFESSSDNNHNGPSVSERLAAVHDPIRRTIVDWQTQHPHIPIVGAIGFSEGALVTTLLLWQQQMGHLPWLPRMSVALLICPWYQDEASQYMRNEVMKNHDDDNDSKDTEWQEELVIRIPTLHLQGRDDFALAGSKMLVARHFSPREAQVLEFAGQHQFPNRPRDVLEVINRFRKLCVTAQTLE
InterPro domains: - IPR050593: Lovastatin nonaketide synthase thioesterase (family) [16-248]
- IPR005645: Serine hydrolase domain (domain) [14-235]
- IPR029058: Alpha/Beta hydrolase fold (homologous_superfamily) [11-251]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0016788 (hydrolase activity, acting on ester bonds)
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:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)