CALK_PENDC
ID CALK_PENDC Reviewed; 371 AA.
AC A0A1V6PAP3;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Trans-enoyl reductase calK {ECO:0000303|PubMed:30598828};
DE EC=1.-.-.- {ECO:0000305|PubMed:30598828};
DE AltName: Full=Calbistrin biosynthesis cluster protein K {ECO:0000303|PubMed:30598828};
GN Name=calK {ECO:0000303|PubMed:30598828}; ORFNames=PENDEC_c013G03312;
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: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of calbistrin A and related compounds. Calbistrin A is
CC a secondary metabolite with an interesting structure that was recently
CC found to have bioactivity against leukemia cells. It consists of two
CC polyketides linked by an ester bond: a bicyclic decalin containing
CC 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 -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:30598828}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
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 zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; MDYL01000013; OQD73827.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1V6PAP3; -.
DR SMR; A0A1V6PAP3; -.
DR OMA; TGTMACQ; -.
DR Proteomes; UP000191522; Unassembled WGS sequence.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NADP; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..371
FT /note="Trans-enoyl reductase calK"
FT /id="PRO_0000446487"
FT BINDING 51..54
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 145..152
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 181..184
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 204..207
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 222
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 269..270
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 289..293
FT /ligand="substrate"
FT /evidence="ECO:0000255"
FT BINDING 359..360
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 371 AA; 39601 MW; 79E9C91304455206 CRC64;
MSSPIQTAIV QTSETSAARL PLRVDRSAPI PQVKSEHHVL VRVLAVALNP NDHKMVTHFN
MPDSIAGCDF CGIVTESSSN GTSLSSSAGA RLPVGTRVCG ALFPYSPEDP DNGSFAQYCV
VDARLLVRVP DSWSDLEAAS LGVGWSTISL AFSDPNALGL EGLPTQPSHR AKEPVLVYGG
GTASGTLACQ LLNLMGYTPI AIASNQSSEL AMKYGASATA CYTSKDCVDT VKSLAGKPIR
RILDCITDAE SAAICYSAMA RSSGTYACLE ECPDACRTRR IIKVKEVMGF QVLGVDIKLG
DSTYTRLGDQ KLMAIGIQWA NEIQALMESG QLKAHPLREL PGGWEAIIEG LEMLRNGEVR
GQKLVVRIPQ E
