Protein: Cytochrome P450 monooxygenase iccC (A0A482NAF7)
Organism: Talaromyces variabilis (Penicillium variabile)
Function: Cytochrome P450 monooxygenase; part of the gene cluster that mediates the biosynthesis of ilicicolin H, a 4-hydroxy-2- pyridonealkaloid that has potent and broad antifungal activities by inhibiting the mitochondrial respiration chain. IccC catalyzes the ring expansion of the tetramate intermediate to the acyclic 2-pyridone intermediate that contains the trans bis-diene chain. The biosynthesis of ilicicolin H starts with formation of the tetramic acid by the hybrid PKS-NRPS synthetase iccA with the partnering trans-enoyl reductase iccB since iccA lacks a designated enoylreductase (ER) domain. The cytochrome P450 monooxygenase iccC then catalyzes the ring expansion of the tetramate to the acyclic 2-pyridone. The pericyclase iccD further converts the acyclic 2-pyridone into 8-epi-ilicicolin H. Finally, the epimerase iccE converts 8-epi-ilicicolin H into ilicicolin H via epimerization. IccA to iccE are sufficient for ilicicolin H biosynthesis and the roles of the remaining enzymes, iccF, iccG and iccH within the pathway have still to be determined (Probable)
Subcellular location: Membrane; Single-pass membrane protein
Sequence: MITLQNLPWILLYTGFLAIFLSRLFSNGKQSRDEKANGCQPPARYPQWDPIMGLDLVYSQVSALKNNRYLEWLRDLHAKMPKTFSLNFFGQRWIYSIEPEILKAVYATNFRDFGVEPIRRHSKGSMPFADKGVNTTDGEDWEFSRLLIKPFFERNVYTDTDRIKVHADHFLSLIPADGETFDAQPLVQRWFLDLTTEFIFGESMGSLAHPERADIAWTMLDVLRGGRLRAQMHRFMWARDWTWWLKAVYKVHDYVNPYIRSTLKELAEREERIKQGLPVGPERTDLVWSMATHLRDEELLRSQLCLIIVPNNDTTSIFISNCLWHLARHPEVWKKLREEVFALGEETPLTFEILRNMKYLNGVLNETHRVIPNNVTQVRACVQDTVLPVGGGPDGKWPVQVRKGDIVSVTKTVMYRDPDYWGSDADEFRPERFDGLRGTWNFLPFGGGPRRCPAQMMSQTEAAYMLCRLARTYSRIEARDPEPYTAVMRIGPSNKTGVKIALYK
InterPro domains: - IPR002974: Cytochrome P450, E-class, CYP52, ascomycetes (family) [150-403]
- IPR017972: Cytochrome P450, conserved site (conserved_site) [445-454]
- IPR001128: Cytochrome P450 (family) [60-475]
- IPR036396: Cytochrome P450 superfamily (homologous_superfamily) [41-504]
- IPR047146: Cytochrome P450, E-class, CYP52, fungi (family) [10-503]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0016705 (oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen), GO:0004497 (monooxygenase activity), GO:0016709 (oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen)
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:0044281 (small molecule metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:0042180 (cellular ketone metabolic process), GO:1901615 (organic hydroxy compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:1901564 (organonitrogen compound metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0046483 (heterocycle metabolic process), GO:0044249 (cellular biosynthetic process), GO:0009404 (toxin metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0030638 (polyketide metabolic process), GO:1901566 (organonitrogen compound biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009403 (toxin biosynthetic process), GO:0009821 (alkaloid biosynthetic process), GO:0019438 (aromatic compound biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0009820 (alkaloid metabolic process), GO:1901617 (organic hydroxy compound biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0042181 (ketone biosynthetic process), GO:0072524 (pyridine-containing compound metabolic process), GO:0030639 (polyketide biosynthetic process), GO:0018958 (phenol-containing compound metabolic process), GO:0043386 (mycotoxin biosynthetic process), GO:0072525 (pyridine-containing compound biosynthetic process), GO:0046189 (phenol-containing compound biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005737 (cytoplasm), GO:0005622 (intracellular anatomical structure)