TWMB_TALWO
ID TWMB_TALWO Reviewed; 2979 AA.
AC A0A2L0P0K3;
DT 07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT 25-APR-2018, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Polyketide synthase-nonribosomal peptide synthetase TwmB {ECO:0000303|PubMed:29343058};
DE Short=PKS-NRPS TwmB {ECO:0000303|PubMed:29343058};
DE EC=6.3.2.- {ECO:0000269|PubMed:29343058};
DE AltName: Full=Wortmanamides biosynthesis cluster protein B {ECO:0000303|PubMed:29343058};
GN Name=TwmB {ECO:0000303|PubMed:29343058};
GN Synonyms=TwnB {ECO:0000303|PubMed:29343058};
OS Talaromyces wortmannii (Penicillium wortmannii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC Talaromyces sect. Islandici.
OX NCBI_TaxID=28567;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, SUBUNIT, AND PATHWAY.
RC STRAIN=ATCC 26942 / CBS 387.67 / CCM F-175 / VKM F-2091;
RX PubMed=29343058; DOI=10.1021/jacs.7b13350;
RA Hai Y., Tang Y.;
RT "Biosynthesis of long-chain N-acyl amide by a truncated polyketide
RT synthase-nonribosomal peptide synthetase hybrid megasynthase in fungi.";
RL J. Am. Chem. Soc. 140:1271-1274(2018).
CC -!- FUNCTION: Polyketide synthase-nonribosomal peptide synthetase; part of
CC the gene cluster that mediates the biosynthesis of wortmanamides A and
CC B, reduced long-chain polyketides amidated with a specific omega-amino
CC acid, 5-aminopentanoic acid (5PA) (PubMed:29343058). The PKS modules of
CC TwmB are involved in the synthesis of the polyketide backbone, whereas
CC the non-canonical C domain of TwmB is a bonafide condensation domain
CC that specifically selects 5PA and catalyzes amidation to release
CC polyketide chain (PubMed:29343058). The C domain clearly prefers C16
CC and C18 fatty acyl substrates, which is consistent with simultaneous
CC formation of both octaketide and nonaketide acyl amides wortmanamides A
CC and B (PubMed:29343058). Because TwmB lacks a designated enoylreductase
CC (ER) domain, the required activity is provided the enoyl reductase TwmE
CC (PubMed:29343058). The roles of the remaining enzymes have still to be
CC clarified (Probable). {ECO:0000269|PubMed:29343058,
CC ECO:0000305|PubMed:29343058}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-aminopentanoate + acetyl-CoA + 17 H(+) + 7 malonyl-CoA + 11
CC NADPH = 7 CO2 + 8 CoA + 6 H2O + 11 NADP(+) + wortmanamide A;
CC Xref=Rhea:RHEA:66808, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:167452, ChEBI:CHEBI:356010;
CC Evidence={ECO:0000269|PubMed:29343058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66809;
CC Evidence={ECO:0000269|PubMed:29343058};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-aminopentanoate + acetyl-CoA + 20 H(+) + 8 malonyl-CoA + 13
CC NADPH = 8 CO2 + 9 CoA + 7 H2O + 13 NADP(+) + wortmanamide B;
CC Xref=Rhea:RHEA:66812, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:167453, ChEBI:CHEBI:356010;
CC Evidence={ECO:0000269|PubMed:29343058};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66813;
CC Evidence={ECO:0000269|PubMed:29343058};
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000269|PubMed:29343058};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000269|PubMed:29343058};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 mM for 5-aminopentanoic acid {ECO:0000269|PubMed:29343058};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:29343058}.
CC -!- SUBUNIT: Interacts with TwmE. {ECO:0000305|PubMed:29343058}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; an inactive
CC methyltransferase (CMeT) domain; a ketoreductase (KR) domain that
CC catalyzes beta-ketoreduction steps; and an acyl-carrier protein (ACP)
CC that serves as the tether of the growing and completed polyketide via
CC its phosphopantetheinyl arm (Probable). A C-terminal thioesterase (TE)
CC domain that is often found in polyketide synthase proteins is not
CC present in this protein, but TwmB contains instead a C-terminal
CC condensation (C) domain that specifically selects 5PA and catalyzes
CC amidation to release polyketide chain (PubMed:29343058). This C domain
CC is a bonafide condensation enzyme despite that the second catalytic
CC histidine in the HHxxxDG motif is substituted by proline
CC (PubMed:29343058). {ECO:0000269|PubMed:29343058,
CC ECO:0000305|PubMed:29343058}.
CC -!- DOMAIN: Lacks an enoylreductase (ER) domain that reduces enoyl groups
CC to alkyl group which function is performed by the trans-acting enoyl
CC reductase TwmE. {ECO:0000305|PubMed:29343058}.
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DR EMBL; MG837519; AUY61970.1; -; Genomic_DNA.
DR EMBL; MH399766; QBC19710.1; -; Genomic_DNA.
DR SMR; A0A2L0P0K3; -.
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:InterPro.
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:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
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; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
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; IPR013216; Methyltransf_11.
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; 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; PF08241; Methyltransf_11; 1.
DR Pfam; PF00550; PP-binding; 1.
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; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Isomerase; Ligase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2979
FT /note="Polyketide synthase-nonribosomal peptide synthetase
FT TwmB"
FT /id="PRO_0000452489"
FT DOMAIN 2380..2465
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 8..438
FT /note="Ketoacyl synthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29343058"
FT REGION 549..864
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29343058"
FT REGION 936..1234
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29343058"
FT REGION 1387..1572
FT /note="Inactive methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29343058"
FT REGION 2098..2271
FT /note="Ketoreductase (KR)domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29343058"
FT REGION 2476..2497
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2534..2970
FT /note="Condensation"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT ACT_SITE 176
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 643
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 968
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2425
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2979 AA; 329219 MW; 4C40041839B0E469 CRC64;
MAGEGAEIAI IGSGCRFPGN ASSPSKLWAL LQNPTSVASK VPALGGYYHE DALYHGHANV
KEAYLLAGEE THRRFDAAFF GIKPSEANVL DPQVRLLLET VYEALEDGGQ PMDSLRGSDT
AVYAGQMVND YELLMYRDLE NLGRYHATGT SRTMVSNRVS FFFDWHGPSM TIDTACSSSL
VALHNAVQQL QSGHSRVAIV AGANLIHDVG SFIAESSLQM LSPNGQSRMW DADADGYARG
EGVAAIVLKT REAAEADGDH IECIIRGTAV NQDGKTPGQT MPSASAQAQL IRDCYARAGL
DLTNSLHRPQ YFEAHGTGTP AGDPIEAEAI SSAFFPGASS SLSIFVGSIK TVVGHTEGTA
GIAGLLKASL ALQNKLIPPN LLFNTLNPRI KPFYDHLHVP TALTPWPSVA SGYPRRASVN
SFGFGGTNAH AILESYSPPS HPTQVLSTVY IPFVFSAFSE ASLKSYLVAF STYLRENKTT
YDLRDIAYSL DARRTRHQVV TTISASTADE LCDSIEKKLE LSRADPDQRV GVRATHQTAE
ARKPRVLGVF TGQGAQWAQM GLELITASAV AKSTVESLQK RLDRLPDADR PTWSLVQELE
RDSSSSHIME AKFSQPLCTA IQILQINLLR AAGIEFTAVV GHSSGEIAAA YAAGRISAED
AICIAYYRGL YSSLAYGLNG KPGAMMAVGT SPEDAEDLLG FPEFEGRACV AAVNSATSVT
ISGDQDALEE LKVVFEDEHK QARFLKVDKA YHSHHMKECS AKYLESLAAL NIQVGSGSQT
SWFSSVYEQE VKGRDFLKGP YWDDNMVEPV LFMQAVDNAC ASTRHFDLAI ELGPHPALKG
PALQTIQERL SHQIPYTGLF TRGVPAITAF SEGLGYCWTH LGQGVVNLQN YDNFISGNLK
CRLVKGLPTY AWDHENEYWH ETRYARAVRM RPGPVHDLLG HLTPNSTDQD MRWRQFLRLP
EVKWVTGHRL QNLTVFPAAG YIVSVIEAAM SLCKDVSVTL IEIIDVDIDS ALVFDNDDVS
IEVIISLTGI TRRENKAIEA DFKYHATSGK DTEPLKLKAS GRVRIHLGEA CPTVLPPRAQ
KPPNLVSVSE KKFYDSISEL GYQYSGQFAS LERIERKLGA ATGFISITEA SKYLIHPGAL
DAAFQSTHLT YAAPEDGESR SIYIPRRIKR LTFNPNLCIH ARNKQTDLAF DASQPIELPH
ANKLCDINLY PEHLDHAIIR VQGLECVPFS RQTAKDDREA FSNIVWDVLD PDVEAITKDY
HSKTSDSLEL AGLLERVAAF YLRSLEKEVP ENHPSRYEAP CKGLLQYASN ISSQSCATRS
QLTQAHWDHD TSEVLTAVCE PYADSIDMKL VFDCGKNLAS SVMGESTAGE VSGLMQEWYR
SGSGVKNFTA HLAGILKQIV HRYPQMHILE VGPEAGAATN VILTEIGPAF ASYTVATSTD
ILFNPEKALP DIYKAKVLPK ELDLSKNPRD QGFTEKSFDV VVASLVLHQS PEFEKCLRNA
RRLLKPGGHL IVLELRPSLP YFLSVIFSAK SHQWFNAEEG RTSFPAITLL EWDSLLRQTG
FSGIDTSTVE QPEIGGPFSI FVSQAMDEKI AFLREPLSTA FPISSPGPTI QDLLILGGNS
LKTARLVNQL SAVLKEHCGS LRTARSMGFV DDISPKTIIL SLTDLDTNEF KQLDESKWDS
LKKIVSHTGT LVWVTHGRLA DNPHANMMLG LLRGSARDNS TLDYLLLDIE EAHRIEHSVI
AEAILRHRAA SQWRESESIS YSVESELVMD KAGRFLIPRL MMNEKMNDRY NSNWREIREP
ARPSLDNIAI SASGSGWDVV LEPLPPVRRA QLRTTHSLLS PIRVTGSGCM YISLCSGLLS
GDKVIALSSK NNSVVCPQDE LSVPVEVPPG SEARFLWLTA HYLLASSILK GLSEEDQVLI
HEPSLEFSTA IENEASMLGV EVTFTTKNQD APDSWMVIHP FSFEQSALAR FEDEIFSVFI
NMAPSQEETE SVADIFATAL PGHCRKESLR SLFGNKAWTP KGSQIKEIQR RLLRAVSWAS
GMLTKSHCDG MTSLAIDVLP GTVGQLEPFA VIEWDTVSEV SVKVQPVDTL VSFSDKKTYW
LVGLTGGLGL SLCEWMVRRG ARYFVISSRQ PNIERGWLDG MHKKGVRVEI SACDLSKRDQ
VEGLYAEICS SMPAIGGVAQ GAMVLEDVAI QNMTLEQLSR VTKPKVDGSI YLNELFQENT
LDFFVFFSSV SSVVGNHGQA NYAAANTFMA SLAEQRRRKG LAASVMDIGA VFGVGYITRS
GNEKLMGKVT LQSGGYVRTS ERDFHQLFGE AVLAGKPGST GPIELVSGVR KVSQREEERP
VWETWPRMSH FVMDHEGPEY TTDASNKAHI PVKVRLAEAR NNEEAYGIVW EDFVRKLQSL
FQIDITSLTK AELGAMRLDQ MGIDSLTAVE IRGWLMKTFE VNLPVLKILN GISVGELVDT
ATEAIPSHLV PNLAGYPAEQ TSSQNSDSGQ DMASSFDTVV NNPFDSDQVS SFHSDLSSNQ
EDATATDSKS TVLKSIPVSF TQARFYPSGL FLEDKVGLNH IAWARFTGEV SAERLQRALH
SLAEQHEILR TAFFDQAGKQ MQHILNTSPV YLEHKQIQNE DEVTELVMSL QKEYVYDVAR
GETMRVILLS RSATENYFIL GVHPLVLDAT SFQIYLKWLA FHYTSPNKIH RVKQFAESSE
QRHADYAAGK FEAELQFWRN EFSTPIKPLP LLTVAKVNER PKLKAYENIR SSLTIEVDTK
TRILDICRRI RATPFHFYLA VLRVLLLQYT AYGDNSEDVT IAVAENGRGY DAEEMDVIGP
LYNLVLVRIL AQQTTRFEDL LETTRNKTYA ALSNSKLPYP MLVEELGLQR IAKDYPFVQV
FADYRVGQRT TAEFGEDNKL VMMGFDFNVP YDVFLDTIDE PEGECLHELF LRNDLFGREE
ADRLARSYKS LVVAFAEHPA MTLGQAALAE SECGGKIAQ
