CALI_PENDC
ID CALI_PENDC Reviewed; 346 AA.
AC A0A1V6PAN1;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2017, sequence version 1.
DT 03-AUG-2022, entry version 19.
DE RecName: Full=Oxidoreductase calI {ECO:0000303|PubMed:30598828};
DE EC=1.-.-.- {ECO:0000305|PubMed:30598828};
DE AltName: Full=Calbistrin biosynthesis cluster protein I {ECO:0000303|PubMed:30598828};
GN Name=calI {ECO:0000303|PubMed:30598828}; ORFNames=PENDEC_c013G00477;
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: Oxidoreductase; part of the gene cluster that mediates the
CC biosynthesis of calbistrin A and related compounds. Calbistrin A is a
CC 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 -!- 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 short-chain dehydrogenases/reductases (SDR)
CC family. {ECO:0000305}.
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DR EMBL; MDYL01000013; OQD73893.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1V6PAN1; -.
DR SMR; A0A1V6PAN1; -.
DR STRING; 69771.A0A1V6PAN1; -.
DR OMA; ATHEGQF; -.
DR Proteomes; UP000191522; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR002347; SDR_fam.
DR Pfam; PF00106; adh_short; 1.
DR PRINTS; PR00081; GDHRDH.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..346
FT /note="Oxidoreductase calI"
FT /id="PRO_0000446479"
FT REGION 11..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 208
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10001"
FT BINDING 44..52
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 71..72
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 99..101
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 182
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 208..212
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
FT BINDING 241..244
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q92506"
SQ SEQUENCE 346 AA; 37767 MW; 94D396503C294E86 CRC64;
MALDRYAALH VSTPQGRGDG RPTADQVLRD QDPLGSHWSD KVILITGGTA GLGAESARVL
HKTGAKIFIM GRDIAKGEKV AADISASNPD YPPIEVIQMD QSRLESVREG AVEFLKRSGG
KLNVLMANAG IVASPVKETQ DGFEAVFAIN YLSTFLLVQL LAPALVASTT PEYNSRLVVV
SSAGHRASNI DPDKYNLVGE GYDPSKAYAR SKTASILMAN EFERRYGDRG VHALSLNPGI
IMDTEISRGL PGTSASRREQ YYKMEPLLAQ YEKDVMQGAA TQVWATVAKE LEGKGGLYLD
DVQVAREATH EGQFCRPGWK PWIWNEDNAV RLWKDSLNMV GLESEN
