Protein: Asnovolin H dehydrogenase nvfC (A0A2I1BSW8)
Organism: Aspergillus novofumigatus (strain IBT 16806)
Function: Short chain dehydrogenase; part of the gene cluster that mediates the biosynthesis of novofumigatonin, a heavily oxygenated meroterpenoid containing a unique orthoester moiety. The first step of the pathway is the synthesis of 3,5- dimethylorsellinic acid (DMOA) by the polyketide synthase nvfA via condensation of one acetyl-CoA starter unit with 3 malonyl-CoA units and 2 methylations. DMOA is then converted to farnesyl-DMOA by the farnesyltransferase nvfB. Epoxydation by FAD-dependent monooxygenase nvfK, followed by a protonation-initiated cyclization catalyzed by the terpene cyclase nvfL leads to the production of asnavolin H. The short chain dehydrogenase nvfC then as a 3-OH dehydrogenase of asnovolin H to yield chemesin D. There are two branches to synthesize asnovolin A from chemesin D. In one branch, chemesin D undergoes Baeyer-Villiger oxidation by nvfH, methylation by nvfJ, and enoyl reduction by the nvfM D enoylreductase that reduces the double bond between C-5'and C-6', to form respectively asnovolin I, asnovolin K, and asnovolin A. In the other branch, the methylation precedes the Baeyer-Villiger oxidation and the enoyl reduction to yield asnovolin A via the asnovolin J intermediate. Asnovolin A is further converted to fumigatonoid A by the Fe(II)/2-oxoglutarate-dependent dioxygenase nvfI that catalyzes an endoperoxidation reaction. The alpha/beta hydrolase nvfD then acts as an epimerase that converts fumigatonoid A to its C-5' epimer, which then undergoes spontaneous or nvfD-catalyzed lactonization. The following step utilizes the ketoreductase nvfG to produce fumigatonoid B. The dioxygenase nvfE further converts fumigatonoid B into fumigatonoid C. Finally the Fe(II)/2- oxoglutarate-dependent dioxygenase nvfF catalyzes two rounds of oxidation to transform fumigatonoid C into the end product, novofumigatonin A
Subcellular location: Membrane; Single-pass membrane protein
Sequence: MGSLHDYVLIITGSASGIGLATATIALDEGARVLGVDISSPPRSLIDHSNFKFVEGNLSLEPTPRRVVEACVKAFGGRIDGLLNIAGVMDLNQSVDSLSDTMWESCIAINLTAPVKLMREVIPIMRQQKSGSIVNVASKAALSGAVSGVAYTASKHGLVGATKNVAWRFKQENIRCNAVCPGAVDGTSIHRGLETSQFDSEALGTMSLIHEAHMRDRERGIHIQPEDIARSLLFLVSSRSNGINGAIIPIDNAWSTI
InterPro domains: - IPR036291: NAD(P)-binding domain superfamily (homologous_superfamily) [1-255]
- IPR051122: SDR DHRS6-like (family) [2-255]
- IPR002347: Short-chain dehydrogenase/reductase SDR (family) [8-238]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity)
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:0071704 (organic substance metabolic process), GO:0044281 (small molecule metabolic process), GO:0044238 (primary metabolic process), GO:0044255 (cellular lipid metabolic process), GO:0042180 (cellular ketone metabolic process), GO:0044249 (cellular biosynthetic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006629 (lipid metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0046483 (heterocycle metabolic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0042181 (ketone biosynthetic process), GO:0006720 (isoprenoid metabolic process), GO:0008299 (isoprenoid biosynthetic process), GO:0008610 (lipid biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0006721 (terpenoid metabolic process), GO:0016114 (terpenoid biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005829 (cytosol), GO:0005622 (intracellular anatomical structure)