Protein: NADH-dependent flavin oxidoreductase iccE (A0A482N8M8)
Organism: Talaromyces variabilis (Penicillium variabile)
Function: NADH-dependent flavin oxidoreductase; 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. IccE acts as an epimerase and catalyzes the conversion of 8-epi-ilicicolin H into the final product ilicicolin H. 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: MADLHLAKSITLRCGLTLPNRLAKTAIAESIAPRNMLIDEGFHRVYAPWAEGGWGMVLTGHVQVDSMHLGTHTDPAVNADFSDDQIVGSWKVWAAVCNRHGTPTIMQLNHPGRQAPIGAGTSGVFAKNISASAVPMDIGSGLLARAVSKIVFGTPREMTVDDIGKLVRQFARAARLASQSGFAGVELHASHGYLLAQFLSAATNRRKDAYGGTPANRARIVVEIIKAVRAEVPASFCVGIILTAVHGSASTEEFQSFIEQAQLICDAGVDFIEISGGTFETPSMFIGPEKRGKAYDWDNQEAFFLDFAQAIRPHLGTVPLLLTGGFRSCHAMEAAVKRGDCDMIGLARPAVVNPLLPKTVVFNPEVNKSGDTKLHATRTPAPWYIKLFGITALNVHMDNAWYVGRLQTLAKTGR
InterPro domains: - IPR051799: NADH-dependent flavin oxidoreductase (family) [2-368]
- IPR013785: Aldolase-type TIM barrel (homologous_superfamily) [4-386]
- IPR001155: NADH:flavin oxidoreductase/NADH oxidase, N-terminal (domain) [16-360]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0016627 (oxidoreductase activity, acting on the CH-CH group of donors), GO:0016628 (oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor)
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:0071944 (cell periphery), GO:0016020 (membrane), GO:0005886 (plasma membrane)