Protein: Trans-enoyl reductase iccB (A0A482N9T9)
Organism: Talaromyces variabilis (Penicillium variabile)
Function: Trans-enoyl reductase; 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. IccB collaborates with the hybrid PKS-NRPS synthetase iccA to assemble the backbone of ilicicolin H. The PKS portion of iccA and trans- acting enoyl reductase iccB work together to construct an octaketide, and two methyl groups are introduced by the MT domain of iccA during the chain assembly. The nascent chain is then condensed with tyrosine, catalyzed by the iliA C domain, and the resulting PKS-NRPS hybrid is offloaded by the iliA RED domain to form an advanced tetramic acid intermediate. 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)
Sequence: MDATLPSIHTALKILGPNNVSVSENTALPVIQPLDILVRVACISINHVDAKSADMSPSPGATSGTDFSGVVVAIGSDVPKESFRSTNGMKPVQIGDRVFGGVFGNNPLRRDNGAFAEYVAVPARLVWHIPGGMDFSTASTLGAAVATVGLSLFQYMQLPMPTTTSTASPDNGPFVLVYGGGTATGAMAIQVLKIAGFRPITTCSSASAGHATELGATATFDYRSPTCGAELREHTGDTLTLALDCITDTASMNICYEALGSSGGRYVALDSFPLRAHTRRSVVPDWVCTYSQFGHPIAWAAPYNLEARPEDLLTAEAWYVVAQKLIDQGLITPHPKEERLGGLAAIGEGMEAVRRGQIKGKKLVYPISNELCAAA
InterPro domains: - IPR036291: NAD(P)-binding domain superfamily (homologous_superfamily) [133-276]
- IPR020843: Enoylreductase domain (domain) [16-364]
- IPR011032: GroES-like superfamily (homologous_superfamily) [5-185]
- IPR047122: Trans-enoyl reductase-like (family) [9-369]
- IPR013149: Alcohol dehydrogenase-like, C-terminal (domain) [184-267]
- IPR013154: Alcohol dehydrogenase-like, N-terminal (domain) [33-130]
Gene Ontology annotations:
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: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)