LCSE_PURLI
ID LCSE_PURLI Reviewed; 316 AA.
AC A0A179H324;
DT 10-APR-2019, integrated into UniProtKB/Swiss-Prot.
DT 07-SEP-2016, sequence version 1.
DT 25-MAY-2022, entry version 13.
DE RecName: Full=Probable thioesterase lcsE {ECO:0000303|PubMed:27416025};
DE EC=3.1.-.- {ECO:0000305|PubMed:27416025};
DE AltName: Full=Leucinostatins biosynthesis cluster protein E {ECO:0000303|PubMed:27416025};
GN Name=lcsE {ECO:0000303|PubMed:27416025}; ORFNames=PCL_01814, VFPBJ_02535;
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].
RC STRAIN=36-1;
RX PubMed=27486440; DOI=10.3389/fmicb.2016.01084;
RA Xie J., Li S., Mo C., Xiao X., Peng D., Wang G., Xiao Y.;
RT "Genome and transcriptome sequences reveal the specific parasitism of the
RT nematophagous Purpureocillium lilacinum 36-1.";
RL Front. Microbiol. 7:1084-1084(2016).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], IDENTIFICATION, FUNCTION,
RP DISRUPTION PHENOTYPE, 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: Probable thioesterase; part of the gene cluster that mediates
CC the biosynthesis of the lipopeptide antibiotics leucinostatins that
CC 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 -!- DISRUPTION PHENOTYPE: Abolishes the production of leucinostatins A and
CC B. {ECO:0000269|PubMed:27416025}.
CC -!- SIMILARITY: Belongs to the AMT4 thioesterase 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; LSBH01000002; OAQ83769.1; -; Genomic_DNA.
DR EMBL; LCWV01000014; PWI68725.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A179H324; -.
DR SMR; A0A179H324; -.
DR EnsemblFungi; OAQ83769; OAQ83769; VFPBJ_02535.
DR Proteomes; UP000078240; Unassembled WGS sequence.
DR Proteomes; UP000245956; Unassembled WGS sequence.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0009058; P:biosynthetic process; IEA:InterPro.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00975; Thioesterase; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 2: Evidence at transcript level;
KW Hydrolase.
FT CHAIN 1..316
FT /note="Probable thioesterase lcsE"
FT /id="PRO_0000446603"
SQ SEQUENCE 316 AA; 34890 MW; D7E15AF9758E9DF9 CRC64;
MAPTDRNPVQ VQYYAKGKKT TESSGPAPAP LILIHDGGGT TFAYFTIGRL ERDVWAIHSP
TFTSAQPWEG GMDGMAKHYI ELIEKVAGIK GKILLGGWSL GGYVALTMAH MIASSPASFE
ISIDGILMMD SPWLVAGRDL PIGTPQPALI GIPDLVRKSL DNCERMLYHW ELPQWGRSSG
KAFKFSAGNE KFETQPGTVL YRSLKGDWRA VERTVSHELT EQQALQTPPS GPPPAVMLRS
VIPAPTKGSS GKPCRVDQFR DELLLGWDGK YNTDMIHAVL EARSHHYDMF NQLYVDEVTE
TIKEAIQIIE TVLPNE
