LUC5_FUSSX
ID LUC5_FUSSX Reviewed; 3926 AA.
AC A0A6J4B487;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 07-OCT-2020, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=Hybrid PKS-NRPS synthetase LUC5 {ECO:0000303|PubMed:32043422};
DE EC=2.3.1.- {ECO:0000305|PubMed:32043422};
DE EC=6.3.2.- {ECO:0000305|PubMed:32043422};
DE AltName: Full=Lucilactaene biosynthesis cluster protein 5 {ECO:0000303|PubMed:32043422};
GN Name=LUC5 {ECO:0000303|PubMed:32043422};
OS Fusarium sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=29916;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, DOMAIN,
RP AND PATHWAY.
RC STRAIN=RK97-94;
RX PubMed=32043422; DOI=10.1080/09168451.2020.1725419;
RA Kato S., Motoyama T., Futamura Y., Uramoto M., Nogawa T., Hayashi T.,
RA Hirota H., Tanaka A., Takahashi-Ando N., Kamakura T., Osada H.;
RT "Biosynthetic gene cluster identification and biological activity of
RT lucilactaene from Fusarium sp. RK97-94.";
RL Biosci. Biotechnol. Biochem. 84:1303-1307(2020).
CC -!- FUNCTION: Methyltransferase; part of the gene cluster that mediates the
CC biosynthesis of the mycotoxin lucilactaene and the lucilactaene-related
CC compound NG-391 that act as cell cycle inhibitors with potent growth
CC inhibitory activity against malarial parasites, moderate growth
CC inhibitory activity against cancer cells, and no activity against
CC bacteria and fungi (PubMed:32043422). Within the cluster, LUC5, LUC6,
CC LUC2 and LUC1 are sufficient for lucilactaene production (By
CC similarity). The roles of the other LUC members are yet undetermined
CC (By similarity). The hybrid PKS-NRPS synthetase LUC5 is responsible for
CC the condensation of one acetyl-coenzyme A (CoA) unit with six malonyl-
CC CoA units and the amide linkage of the arising heptaketide and
CC homoserine, subsequently releasing the first intermediate, as an
CC alcohol with an open ring structure (By similarity). Lucilactaene and
CC NG-391 lack the 7-methyl group present in fusarins which is inserted in
CC fusarins by the C-methyltransferase (CMeT) domain of the fusarin
CC synthetase FUS1, suggesting that the CMet domain of LUC5 does not
CC methylate this position (Probable). The cytochrome P450 monooxygenase
CC LUC2 participates in multiple oxidation processes at carbon C-20 and is
CC able to use the LUC5 product as substrate (By similarity). This
CC reaction seems to be essential before the 2-pyrrolidone ring closure
CC can be catalyzed by LUC6 (By similarity). LUC2 is able to further
CC oxidizes carbon C-20 after ring closure, resulting in the formation of
CC demethyllucilactaene (By similarity). As the last step, the
CC methyltransferase LUC1 methylates the hydroxyl group at C-21 to
CC generate lucilactaene (PubMed:32043422). {ECO:0000250|UniProtKB:S0EEY3,
CC ECO:0000269|PubMed:32043422, ECO:0000305|PubMed:32043422}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:32043422}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC are present within the NRP synthetase. LUC5 contains also polyketide
CC synthase modules including a ketosynthase (KS) domain, a malonyl-
CC CoA:ACP transacylase (MAT) domain, a dehydrogenase (DH) domain, a C-
CC methyltransferase (CMeT) domain, and a ketoreductase (KR) domain. LUC5
CC has the following architecture: KS-MAT-DH-CMet-KR-T-C-A-T-TE.
CC {ECO:0000305|PubMed:32043422}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of lucilactaene and NG-
CC 391. {ECO:0000269|PubMed:32043422}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; LC515193; BBQ09587.1; -; Genomic_DNA.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE 3: Inferred from homology;
KW Isomerase; Ligase; Methyltransferase; Multifunctional enzyme;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..3926
FT /note="Hybrid PKS-NRPS synthetase LUC5"
FT /id="PRO_0000454637"
FT DOMAIN 2371..2448
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3501..3580
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 11..442
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 545..863
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 932..1225
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1344..1572
FT /note="C-methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT REGION 2091..2265
FT /note="Ketoreductase (KR) domain 1"
FT /evidence="ECO:0000255"
FT REGION 2474..2518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2525..2810
FT /note="Condensation"
FT /evidence="ECO:0000255"
FT REGION 2979..3389
FT /note="Adenylation"
FT /evidence="ECO:0000255"
FT REGION 3619..3840
FT /note="Thiolester reductase (TE) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 2474..2513
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2408
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3540
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3926 AA; 430005 MW; E0CB1F128F5A6383 CRC64;
MGAPNSTREP IAIVGTACRF PGGANTPSKL WDLLCEKRDV QTRIPPERFN PDAFYHRNGE
KSGCTDVKKA YLLTEDIRAF DASFFKINPR EAEAMDPQQR LLLETVYEAT EAAGLPYEDL
KGSNTAVYVG SMTGDYHEML LRDPQDMPKY MATGTARSIL SNRVSYFFDW KGPSMTIDTA
CSSSLVAVHE AVTALRLGVS NIACAAGTNL ILGPEMMISE SKLHMLSPTG RSKMWDASAN
GYARGEGTAA IMMKTLSQAL SDGDHVYGII RETGVNSDGH TNGITLPSSE SQKTLIRQTY
ANAGLDLIKE RCQFFEAHGT GTPAGDPIEA RAIHEAFFED AAGSSDQMFV GSVKTAIGHL
EGCAGLAGLI KALEAVRRGV IPPNQLFENL NPALKPFAGN LSIPTETLPW PEVAPGTPRR
ASVNSFGFGG TNAHAIIESF DNTPQPAPTG GIISYPLVLS ANSEKSLRRQ ISQLHDTLQN
AGEGEVQDTL YTLAQRRSQL PARTYFSGHT QEELLKKLSA ASAEDATITV ASQEVTNQNS
RILGVFTGQG AQWPTMGREI LKSSAFAGDL ITRLETSLAS LQEPPTWTLS EQILADPESS
RLGEAAVSQP VCTAVQLMLV ELLRQAGITF STVIGHSSGE IAAAYAAGFL TPEDAIRIAY
CRGVCAKLAG GEEGQKGSMM AVGLSYEEAA CFCEDHFPGC IDVAASNAPS SATLSGDKDA
ILEAKALLDE QGTFARVLKV DTAYHSRHMQ PCAEPYMALL RESNIQLLPG DDSCEWFSSV
IGERMSSFTH GQLLTGEYWV ENMVKPVLFT LASELAADSK LPCHVALEVG PHPALKGPFS
QTYKRATGSQ LPYQGALTRN VHDVEALSDA LGFIWARLGK SAVNFASHAE LFSVSKTSFS
TNLPSYPWDH SQSFWKESRK SANFRQRTSP PHPLLGTRST EDATQDLRWL NILHLDDAPW
LEGHKVEGLV VYPAAAYLVM AMESAKSIDE TKTIQLVELF DVQILSAIQL SQDSQGVETL
FTLEIDDVNS TAATARWSLF TSMVGRGSNW KCNAKGHLRV DFGSEAQDSL LPSRDPPVAS
LTSVNIERFY TSLAEIGLGY TGAFKHLATV QRQSGFATAK ASQMNTDFSA MIHPALLDSA
FQSLFAAYCW PDDGSLAAPF VPTFFKSLRI VSLDHIENGQ ELTIDSYLTD TNDREITADL
DIFTSDSEKP LLQLQGLTCT SLLRPGPSNA KELYTQTKWE VDISCAVASL DVQQHDAAED
LDLVDLCERL SYYYLRELNR KVDRSEVPAM DWHFQRIFEW IDYLFPIIEA GKHTTIRKEW
SADEGSWLLE QASKFPGQVD LLLIRAVGEN LTEVVRKETT MLEHMVRNDV LNRFYKFGLG
FQRANGYLSR ISKQIAHRYP QMKILEIGAG TGGATKGILE SLGTTFESYT FTDISTGFFE
AAAEAFEPWV SKIIFKPLNV ENDPVEQGFL EAQYDFIVAS NVLHATKSLS TTMRNVRRLL
KPGGQLLLLE VTSDIVRVRL MMSGLSGWWL GGDDGRRYAP TITVPEWDSL LRSTGFSGVD
HTVNDFYDPS KYMTSVMLSQ AVDDHHVDIL RKPLNSALGW LPQRCITIIG GKNNEIAQQV
SKTLLSMKSA SLDLINHVDS FEQLASTPEL PLRAVLILED LDEPVLKSLT SEKLAGLQRT
INDSRQILWV SKGCQKDEPY ANMSTGLCRS LASEYPHIQL QHIDMETGLD SLAVSRIVEA
LIRIVYKASL KQDDDLLWSH EAELILEDEG RWLIPRILPD DKLNDHLNAG KMKVKTNASL
ADTPVEIQQA GSQWVISQTV PSLPISDNTD HIRIKASYST LHAVRVRGSR VYLSYGHRVT
GSTTPVIAFS ETAGSIISVP ESQVFDVPQG FDIDQSASLR SLVLTAIVES VLAECDHGAA
IIVHEADNYL GAAFETKCRE IGLKLVRTTS KSDHKDDAIF IHPLAPERVV KKALPHVEVA
VVVDLSGRDY SVVDSPLRRH VPSTTKFLEL SDLIGSVTCG LRDVNIQCVQ DAIESSFKSP
SDGPVVNISE VSGLQASETS YATVVDWSIE KPVSVQVQPL QANRLLRSDR TYLLAGCTGG
LGKALCRWMV AAGVRHLALT TRNVEAIDKV WLEGLQLQGA DVRLFQVDVG DKAALERAHA
QVTAEMPPIC GVANAAMVLS DRSFGELKVG DFDKVFGPKV RGTQNLHELF QDEPLDFFIM
FSSLASVVGN RGQANYAAAN LFMTAVAEQR RAKNLAASVI HIGMILGVGY VSSTGAYEAT
LRQYNYMPIS EPDFLNMFSE AILVGQPGSS HAPELITGLN RYSLQEDAPK FFWHENMRFS
HHTLEEQHQE STSTTKASIS QRLAQVQTPA EMLEVVEEEF CTKLERMLQA ESGTIKVSQP
LMSLGVDSLI AAEIRSWFFK ELDVDMPVLE ILNTASVAEI CSTAVASLAT LAPQEQTETT
TLVTSEAVQS LNAVSGNGSS SSRAPTEFNS STLKSGAQST QGTSVSGDKD TNSVDGSAKV
ERNGPLSFAQ ERIWFLQQYL QDATTFNVTM AYRITGPLRV NDLESAFQKV IQRHESLRTG
FHMDPETTVP TQIVYEQSPF GLEQRNDSDI TKEFEELQNT HYDLENGRVL KAIVLTKPDT
DEHILLVGFH HIALDGFSAQ ILVRDLAIAY AGGNLAPLDK GYLDFAVDQR AAVYPAETLQ
YWKTEFETLP PALPVFDFAE TKTRLPLTDY KTRVSERTLQ PDVAGKAKSA ARALAATPFH
VYLAALQVLL SDFASTQDVC IGITDANKND AAHMDTIGFF VNLLPLRFQL SASQTLAELV
SNTKAKANGA LTHSRLPFDV LLDELKIPRS TSHSPLFQVV LNFKMGSTQK VPLADCQAEV
IDFKDVNNPY DLAFDIETYP DGSTSISVKS QEYLYTKNEL DLILESYINL LSLFEKDSSK
TLGEVSQCTP DEAQKTLTLG RGERIPSPSF DTLSHYFEDW VKRQPDAIAI RDDQGTTLSY
SQLKSFVNNI AATLEKSGLT PGARVGVYCE PSIFIIASLL AIAEVGGVYV PLDPQNPIKR
LQLIVDDCEP EILLFDESTK ELAPKLQTNA SLINIYNVRR LPSSAAITNR AQGAGMAYMF
YTSGTTGVPK GVALTHANLV HHIDSITHFY DIKRGTMLQQ APLGFDMSLT QMSLSTMLGG
TLVVASSEAR KDPLQLAKLM LSERVTHTFM TPTLAVALIH HGYEYLVKCV GWEFSLLSGE
AFRTHVISEF QRLGLPQLKL FNGYGPTEIT INSSSGLNEL DLAAPRDTRN PTIGFTLPNY
SCYILDEDLK PVRPGHAGEL FVGGAGIAVG YLRRDELNKE RFLSDPFASS EDVARGWARM
YRTGDKAKFL PDGRIVFLGR IAGDSQIKLR GFRIELEDIA NTIVKSSGGV VSEAAVSFRQ
GVNGPDDGAF LVAFAIISQA HRPENPSSFL KQLLKDLSLP RYMIPAKIVQ VEHLPMGPTG
KLDQNALDVM PIPQDENVHE ETLTTTQERL RALWFESLPA VAPDAFIGSE TDFFEAGGNS
LRIVMLREHI AREFGVMVSV FDLFQASTLG GMAAKIDGST GADNQPIIWE EETRVDIPSG
LETPDEPAIL DGDELEVALT GATGFLGLAI LRSLLKDERI SRVHCLAVRS PSKARDEVFK
SPRVVVYHGD LSSPRLGLSE DEFGTLSKKF DIIIHNGAEV SFLKSYQALK KANVSSTKEL
AQLASGRQIP FHFVSTGGVV NLTDHDGLPE ISVSGFKPPI DGTEGYAASK WASEVILESH
AERAHLPVWI HRPANVTGAA APATDLMGSI LQYSTTMQSL PEISNWKGSF DFVPVEQVAD
EIAASIHESR SSEPVYRHHC GDQKISVSEL SAHLEAGIGA KMEIIGVDDW LARARSTGID
ETTALLVEKM LSGENGGTVP WLRKGE
