CALE_PENDC
ID CALE_PENDC Reviewed; 517 AA.
AC A0A1V6PB34;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Cytochrome P450 monooxygenase calE {ECO:0000303|PubMed:30598828};
DE EC=1.-.-.- {ECO:0000269|PubMed:30598828};
DE AltName: Full=Calbistrin biosynthesis cluster protein E {ECO:0000303|PubMed:30598828};
GN Name=calE {ECO:0000303|PubMed:30598828}; ORFNames=PENDEC_c013G04259;
OS Penicillium decumbens.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=69771;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=IBT 11843;
RX PubMed=28368369; DOI=10.1038/nmicrobiol.2017.44;
RA Nielsen J.C., Grijseels S., Prigent S., Ji B., Dainat J., Nielsen K.F.,
RA Frisvad J.C., Workman M., Nielsen J.;
RT "Global analysis of biosynthetic gene clusters reveals vast potential of
RT secondary metabolite production in Penicillium species.";
RL Nat. Microbiol. 2:17044-17044(2017).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=8436557; DOI=10.7164/antibiotics.46.34;
RA Jackson M., Karwowski J.P., Humphrey P.E., Kohl W.L., Barlow G.J.,
RA Tanaka S.K.;
RT "Calbistrins, novel antifungal agents produced by Penicillium restrictum.
RT I. Production, taxonomy of the producing organism and biological
RT activity.";
RL J. Antibiot. 46:34-38(1993).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=24287995; DOI=10.3390/molecules181214629;
RA Bladt T.T., Duerr C., Knudsen P.B., Kildgaard S., Frisvad J.C.,
RA Gotfredsen C.H., Seiffert M., Larsen T.O.;
RT "Bio-activity and dereplication-based discovery of ophiobolins and other
RT fungal secondary metabolites targeting leukemia cells.";
RL Molecules 18:14629-14650(2013).
RN [4]
RP IDENTIFICATION, FUNCTION, INDUCTION, AND PATHWAY.
RX PubMed=30598828; DOI=10.1186/s40694-018-0063-4;
RA Grijseels S., Pohl C., Nielsen J.C., Wasil Z., Nygaard Y., Nielsen J.,
RA Frisvad J.C., Nielsen K.F., Workman M., Larsen T.O., Driessen A.J.M.,
RA Frandsen R.J.N.;
RT "Identification of the decumbenone biosynthetic gene cluster in Penicillium
RT decumbens and the importance for production of calbistrin.";
RL Fungal Biol. Biotechnol. 5:18-18(2018).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of calbistrin A and related compounds.
CC Calbistrin A is a secondary metabolite with an interesting structure
CC that was recently found to have bioactivity against leukemia cells. It
CC consists of two polyketides linked by an ester bond: a bicyclic decalin
CC containing polyketide and a linear 12 carbon dioic acid structure
CC (PubMed:30598828). The polyketide synthase calA is probably responsible
CC for forming the decalin moiety. Because calA lacks a designated
CC enoylreductase (ER) domain, the required activity is provided by the
CC trans-enoyl reductase calK (PubMed:30598828). Following release from
CC the PKS, calF then probably catalyzes the oxidation and the subsequent
CC Diels Alder cycloisomerization that lead to the formation of the
CC decalin moiety (Probable). The decalin polyketide backbone includes two
CC C-methyl groups, at C7 and C11 in backbone, of which the C7 position is
CC probably methylated by the methyltransferase domain of calA. A
CC candidate for adding the methyl group at C11, if not done by CalA, is
CC the cluster methyltransferase calH (Probable). Several additional
CC tailoring enzymes within the cluster could be involved in the
CC modification of the decalin polyketide product. Those include the 3
CC cytochrome P450 monooxygenases CalE, CalG and CalL, of which one might
CC be responsible for the introduction of the extra hydroxyl group
CC attached to the backbone of the decalin moiety, at position C9 in the
CC backbone, that allows for attachment of the linear moiety (Probable).
CC One tailoring enzyme activity that is expected to be involved in
CC biosynthesis of calbistrin is an acyltransferase for connecting the two
CC polyketide synthase products, and which could be performed by the
CC cluster acyltransferase calJ (Probable). The enzyme responsible for the
CC biosynthesis of the linear moiety, probably a second PKS, has not been
CC identified yet (Probable). {ECO:0000269|PubMed:30598828,
CC ECO:0000305|PubMed:30598828}.
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:30598828}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced in complex medium (Czapek yeast
CC autolysate medium) supporting calbistrin production.
CC {ECO:0000269|PubMed:30598828}.
CC -!- BIOTECHNOLOGY: Calbistrin A has been reported to possess a number of
CC interesting bioactivities including antifungal active against Candida
CC albicans and cytotoxic toward both healthy and leukemic human cells.
CC {ECO:0000269|PubMed:24287995, ECO:0000269|PubMed:8436557}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MDYL01000013; OQD73977.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1V6PB34; -.
DR SMR; A0A1V6PB34; -.
DR OMA; LAMTSMH; -.
DR OrthoDB; 572303at2759; -.
DR Proteomes; UP000191522; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..517
FT /note="Cytochrome P450 monooxygenase calE"
FT /id="PRO_0000446458"
FT TRANSMEM 14..34
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 458
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 8
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 517 AA; 58396 MW; D4033F13E575B9B8 CRC64;
MDLHLDENLS TMDSLMHHYI LIAILVASII AMVVSSYGRE HPLSKVPLVT EKSFWDFTGK
KARDNFAANA RAVIKQGFAK VGASKPFRII SDQGEMLILP PALAHDIRNV DALSHAEFMK
DTTCAEVPGF EPYLESTGTT LLTDMTKTKL MSAMKWLTTP LSNSVAKSCR DLFPEDDEWH
EVVLKDKLLD LIARLSSVIF LGEEEIREDP AWLRITKEYT VDSFIASHQL RPYPRYLRPF
IARFLPQAQK VQAQLREAEA IITPVIERRR AEKAASTTTV ERYDSIEWLE QVAEEKGIKY
SPAAMQLTLA LSAIHTTTDL LTTTMYEILQ HPETIQLLRD EVASVVGDGR LKHSSLYNLK
LMDSVIKEAQ RLKPVLSINM VRMATEDIDL PDGLNIPRGT RLGVSSHASW DPKVFPNPEK
FDPYRFVRLR EQPGEENVWQ LTTTRPEQIA FGHGQHACPG RFLAANEVKI ALCHLLLKYD
WELSSITMPT AISHGIMLDS DPTVKVNVRS RQSEVVL
