ID   CALJ_PENDC              Reviewed;         418 AA.
AC   P0CU81;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   10-APR-2019, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=Acyltransferase calJ {ECO:0000303|PubMed:30598828};
DE            EC=2.3.1.- {ECO:0000305|PubMed:30598828};
DE   AltName: Full=Calbistrin biosynthesis cluster protein J {ECO:0000303|PubMed:30598828};
GN   Name=calJ {ECO:0000303|PubMed:30598828};
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: Acyltransferase; 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 class-A beta-lactamase family.
CC       {ECO:0000305}.
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DR   EMBL; MDYL01000013; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; P0CU81; -.
DR   SMR; P0CU81; -.
DR   Proteomes; UP000191522; Unassembled WGS sequence.
DR   GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.710.10; -; 1.
DR   InterPro; IPR001466; Beta-lactam-related.
DR   InterPro; IPR012338; Beta-lactam/transpept-like.
DR   Pfam; PF00144; Beta-lactamase; 1.
DR   SUPFAM; SSF56601; SSF56601; 1.
PE   1: Evidence at protein level;
KW   Acyltransferase; Hydrolase; Reference proteome; Transferase.
FT   CHAIN           1..418
FT                   /note="Acyltransferase calJ"
FT                   /id="PRO_0000446486"
FT   ACT_SITE        79
FT                   /note="Acyl-ester intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
FT   BINDING         176
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
FT   BINDING         191
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9Y7D1"
SQ   SEQUENCE   418 AA;  45973 MW;  E15C8395E0380CB9 CRC64;
     MSDFDALLAN YTSKETPKVH GVICKCVDRH GICPTPHLAK RDLRLTLLGN EIYSKVAGYD
     SVLPGASPLR EDVVLKVASA TKLITSIALL QCIDKGLIDL DEPVTKVLPE FDQKQILTDV
     SGSDLVLEPS KTPITARHLL THTSGLGYPF THRLLRLRAE VRNRAGVSPS LRVTERYEMP
     LVFEPGTGWL YGCSLDWAGV IVSRLHGGIS LEQYFVENIW QRLGLSEPFP CFNIARHPEY
     NARVMGGAIQ TPEGRLQPKD HWAFDNPEDQ DGGSGLSCTT KDYVAVLADL VSDSPKLLKP
     ATIAEMFTPQ LEAKSPGVQM LLGLRPAWDT VSGPIAENAI NHGLGGVLCM DDVPEIDQPK
     GMLGWGGASN IVWWVNRELR VAGFFATQQA PFGNPSVTRL VNAWKKDFWA QFKTIDHA