ID   LCSR_PURLI              Reviewed;         400 AA.
AC   A0A179HLJ8;
DT   10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT   07-SEP-2016, sequence version 1.
DT   25-MAY-2022, entry version 20.
DE   RecName: Full=Metal-dependent hydrolase lscR {ECO:0000303|PubMed:27416025};
DE            EC=3.-.-.- {ECO:0000305|PubMed:27416025};
DE   AltName: Full=Leucinostatins biosynthesis cluster protein R {ECO:0000303|PubMed:27416025};
GN   Name=lcsR {ECO:0000303|PubMed:27416025}; ORFNames=VFPBJ_02534, VFPFJ_04707;
OS   Purpureocillium lilacinum (Paecilomyces lilacinus).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Ophiocordycipitaceae; Purpureocillium.
OX   NCBI_TaxID=33203;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], IDENTIFICATION, FUNCTION,
RP   INDUCTION, AND PATHWAY.
RC   STRAIN=PLBJ-1;
RX   PubMed=27416025; DOI=10.1371/journal.ppat.1005685;
RA   Wang G., Liu Z., Lin R., Li E., Mao Z., Ling J., Yang Y., Yin W.B., Xie B.;
RT   "Biosynthesis of antibiotic leucinostatins in bio-control fungus
RT   Purpureocillium lilacinum and their inhibition on phytophthora revealed by
RT   genome mining.";
RL   PLoS Pathog. 12:E1005685-E1005685(2016).
CC   -!- FUNCTION: Metal-dependent hydrolase; part of the gene cluster that
CC       mediates the biosynthesis of the lipopeptide antibiotics leucinostatins
CC       that show extensive biological activities, including antimalarial,
CC       antiviral, antibacterial, antifungal, and antitumor activities, as well
CC       as phytotoxic (PubMed:27416025). Leucinostatin A contains nine amino
CC       acid residues, including the unusual amino acid 4-methyl-L-proline
CC       (MePro), 2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (AHyMeOA), 3-
CC       hydroxyleucine (HyLeu), alpha-aminoisobutyric acid (AIB), beta-Ala, a
CC       4-methylhex-2-enoic acid at the N-terminus as well as a N1,N1-
CC       dimethylpropane-1,2-diamine (DPD) at the C-terminus (Probable). The
CC       biosynthesis of leucinostatins is probably initiated with the assembly
CC       of 4-methylhex-2-enoic acid by a reducing PKS. Two reducing polyketide
CC       synthases, lcsB and lcsC, have been identified in the cluster and it is
CC       not clear which is the one that assembles 4-methylhex-2-enoic acid
CC       since both contain KS, AT, DH, cMT, ER, KR and ACP domains (Probable).
CC       The polyketide residue might be transferred to the NRPS lcsA, mediated
CC       by two additional enzymes, the acyl-CoA ligase lcsD and the
CC       thioesterase lcsE. The linear polyketide carboxylic acid, which is
CC       released from PKS, is converted to a CoA thioester by lcsD, and then
CC       lcsE hydrolyzes the thiol bond and shuttles the polyketide intermediate
CC       to lcsA (Probable). The C domain of the first module catalyzed the
CC       condensation of 4-methylhex-2-enoic acid and MePro carried by domain
CC       A1, followed by successive condensations of nine amino acids to trigger
CC       the elongation of the linear peptide. A5 and A6 domains of lcsA are
CC       proposed to incorporate leucine, A2 AHyMeOA, and A3 incorporates HyLeu.
CC       A4, A7 and A8 incorporate AIB (Probable). The AHyMeOA in leucinostatin
CC       A activated by the A2 might be produced by the second PKS (lcsB or
CC       lcsC) present within the cluster (Probable). The MePro is probably
CC       produced via leucine cyclization and may originate from a separate
CC       pathway, independent of the cluster. Another nonproteinogenic amino
CC       acid, beta-Ala, could be produced by an aspartic acid decarboxylase
CC       also localized outside of the cluster. Two candidates are VFPBJ_01400
CC       and VFPBJ_10476 (Probable). The final peptide scaffold may be released
CC       by the NAD(P)H-dependent thioester reductase (TE) at the C-terminal
CC       region of lcsA (Probable). Transamination of the lcsA product by the
CC       transaminase lcsP may produce DPD at the C-terminus (Probable). Further
CC       hydroxylation steps performed alternatively by the cytochrome P450
CC       monooxygenases lcsI, lcsK and lcsN then yield the non-methylated
CC       leucinostatins precursor. It is also possible that leucines can be
CC       hydroxylated prior to their incorporation into the peptide (Probable).
CC       Varying extents of methylation then lead to the formation of
CC       leucinostatins A and B (Probable). {ECO:0000269|PubMed:27416025,
CC       ECO:0000305|PubMed:27416025}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:27416025}.
CC   -!- INDUCTION: Expression is positively regulated by the leucinostatins
CC       biosynthesis cluster-specific transcription regulator lcsF.
CC       {ECO:0000269|PubMed:27416025}.
CC   -!- SIMILARITY: Belongs to the UPF0173 family. {ECO:0000305}.
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DR   EMBL; LSBH01000002; OAQ83768.1; -; Genomic_DNA.
DR   EMBL; LSBI01000004; OAQ90548.1; -; Genomic_DNA.
DR   RefSeq; XP_018179267.1; XM_018321787.1.
DR   AlphaFoldDB; A0A179HLJ8; -.
DR   SMR; A0A179HLJ8; -.
DR   STRING; 33203.A0A179HLJ8; -.
DR   EnsemblFungi; OAQ83768; OAQ83768; VFPBJ_02534.
DR   EnsemblFungi; OAQ90548; OAQ90548; VFPFJ_04707.
DR   GeneID; 28886836; -.
DR   KEGG; plj:VFPFJ_04707; -.
DR   OrthoDB; 1194556at2759; -.
DR   Proteomes; UP000078240; Unassembled WGS sequence.
DR   Proteomes; UP000078340; Unassembled WGS sequence.
DR   GO; GO:0070290; F:N-acylphosphatidylethanolamine-specific phospholipase D activity; IEA:InterPro.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   Gene3D; 3.60.15.10; -; 1.
DR   InterPro; IPR001279; Metallo-B-lactamas.
DR   InterPro; IPR024884; NAPE-PLD.
DR   InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR   Pfam; PF12706; Lactamase_B_2; 1.
DR   PIRSF; PIRSF038896; NAPE-PLD; 1.
DR   SUPFAM; SSF56281; SSF56281; 1.
PE   2: Evidence at transcript level;
KW   Hydrolase; Reference proteome.
FT   CHAIN           1..400
FT                   /note="Metal-dependent hydrolase lscR"
FT                   /id="PRO_0000446614"
FT   REGION          1..31
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   400 AA;  44588 MW;  037A0EA1B11E0907 CRC64;
     MTKDLLDVSV DKAVDSPAPK GAEAKVHHHK NGKKVFHNPW PSWHDLDPEA VKAHLKQRKW
     MSTWTHPSTA EAKIPFQTPT LSRERFSNGT SDVRATWLGH ACYFVEFPSG LRVLFDPVMT
     DRCSPSQWFG PRRFTQLPCA VKDIPFLDAV VISHNHYDHL SHPTVVEIAK LHPKAHFFVP
     LGNESWFHAS GITDVTELDW WEGADLTLSS PGQSDRKIEP IRARITCLPA QHTTGRAPWG
     TDKTLWASWS VASPPPDQSG TGNTVASVFF GGDTGYRAVP TLDAQDDDWD EKYADLPVCP
     AFEQIGELYG PFTLGLLPIG AYEPRALMAP IHANPRDAVE IFIDTQCKRA LAMHWGTWVL
     GDEDVREPPQ RLEEALAFKG LARKGVFDVC GLGEVIRIPL