MPCA_MORAP
ID MPCA_MORAP Reviewed; 5532 AA.
AC P0DUV3; A0A7S6VMM6;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 1.
DT 03-AUG-2022, entry version 4.
DE RecName: Full=Malpicyclin synthetase {ECO:0000303|PubMed:33158886};
DE EC=6.3.2.- {ECO:0000269|PubMed:33158886};
DE AltName: Full=Nonribosomal peptide synthetase mpcA {ECO:0000303|PubMed:33158886};
DE Short=NRPS mpcA {ECO:0000303|PubMed:33158886};
GN Name=mpcA {ECO:0000303|PubMed:33158886};
OS Mortierella alpina (Oleaginous fungus) (Mortierella renispora).
OC Eukaryota; Fungi; Fungi incertae sedis; Mucoromycota; Mortierellomycotina;
OC Mortierellomycetes; Mortierellales; Mortierellaceae; Mortierella.
OX NCBI_TaxID=64518;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DOMAIN, CATALYTIC ACTIVITY,
RP AND INDUCTION.
RX PubMed=33158886; DOI=10.1128/aem.02051-20;
RA Wurlitzer J.M., Stanisic A., Wasmuth I., Jungmann S., Fischer D., Kries H.,
RA Gressler M.;
RT "Bacterial-like nonribosomal peptide synthetases produce cyclopeptides in
RT the zygomycetous fungus Mortierella alpina.";
RL Appl. Environ. Microbiol. 87:0-0(2021).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=30789272; DOI=10.1021/acs.orglett.9b00193;
RA Baldeweg F., Warncke P., Fischer D., Gressler M.;
RT "Fungal Biosurfactants from Mortierella alpina.";
RL Org. Lett. 21:1444-1448(2019).
RN [3]
RP FUNCTION.
RX PubMed=33918813; DOI=10.3390/jof7040285;
RA Koczyk G., Pawlowska J., Muszewska A.;
RT "Terpenoid biosynthesis dominates among secondary metabolite clusters in
RT mucoromycotina genomes.";
RL J. Fungi 7:0-0(2021).
CC -!- FUNCTION: Nonribosomal peptide synthetase that catalyzes the
CC biosynthesis of the cyclopentapeptides malpicyclins, natural products
CC that show a moderate antibacterial activity against Gram-positive
CC bacteria as well as biosurfactant activities (PubMed:33158886)
CC (Probable). Modules 1 and 2 show promiscuous adenylation leading to the
CC parallel production of multiple products from one NRPS assembly line,
CC including malpicyclin A corresponding to cyclo(-D-Leu-L-Tyr-D-Arg-D-
CC Val-L-Leu-), malpicyclin B corresponding to cyclo(-D-Ile-L-Tyr-D-Arg-D-
CC Val-L-Leu-), malpicyclin C corresponding to cyclo(-D-Leu-L-Phe-D-Arg-D-
CC Val-L-Leu-) and malpicyclin D corresponding to cyclo(-D-Val-L-Phe-D-
CC Arg-D-Val-L-Leu-) (PubMed:33158886). {ECO:0000269|PubMed:33158886,
CC ECO:0000305|PubMed:33918813}.
CC -!- INDUCTION: Expression is induced in the presence of fructose.
CC {ECO:0000269|PubMed:33158886}.
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. Contains
CC bacterial-like dual epimerase/condensation domains allowing the
CC racemization of enzyme-tethered L-amino acids and the subsequent
CC incorporation of D-amino acids into the metabolites. MpcA has the
CC following architecture: C-A-T-E/C-A-T-C-A-T-E/C-A-T-E/C-A-T-TE.
CC {ECO:0000305|PubMed:33158886}.
CC -!- BIOTECHNOLOGY: Mortierella alpina biosurfactants may have an enormous
CC potential for various applications in pharmacy, health care, food,
CC cosmetics, or textiles since they offer a highly biocompatible and
CC biodegradable alternative for synthetic surfactants in formulations.
CC {ECO:0000269|PubMed:30789272}.
CC -!- MISCELLANEOUS: The surprising structural and mechanistic similarity to
CC bacterial nonribosomal peptide synthetases (NRPSs) points to an
CC endobacterial origin of the Mortierella mpcA and mpbA genes that differ
CC from their asco- and basidiomycete counterparts and may have evolved
CC independently. {ECO:0000269|PubMed:33158886}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; MT800760; QOW41315.1; -; Genomic_DNA.
DR SMR; P0DUV3; -.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0043604; P:amide biosynthetic process; IEA:UniProt.
DR GO; GO:1901566; P:organonitrogen compound biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 4.
DR Gene3D; 3.30.300.30; -; 5.
DR Gene3D; 3.30.559.10; -; 4.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR020802; PKS_thioesterase.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR001031; Thioesterase.
DR Pfam; PF00501; AMP-binding; 5.
DR Pfam; PF13193; AMP-binding_C; 5.
DR Pfam; PF00668; Condensation; 5.
DR Pfam; PF00550; PP-binding; 5.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00823; PKS_PP; 5.
DR SMART; SM00824; PKS_TE; 1.
DR SUPFAM; SSF47336; SSF47336; 5.
DR SUPFAM; SSF53474; SSF53474; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 5.
DR PROSITE; PS00455; AMP_BINDING; 4.
DR PROSITE; PS50075; CARRIER; 5.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 5.
PE 1: Evidence at protein level;
KW Isomerase; Ligase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Repeat.
FT CHAIN 1..5532
FT /note="Malpicyclin synthetase"
FT /id="PRO_0000453666"
FT DOMAIN 897..971
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1997..2071
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3053..3127
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 4130..4204
FT /note="Carrier 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 5209..5284
FT /note="Carrier 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 130..375
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 418..819
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 1017..1464
FT /note="Dual epimerase/condensation (E/C) domain 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 1506..1919
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 2091..2533
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 2574..2975
FT /note="Adenylation 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 3177..3611
FT /note="Dual epimerase/condensation (E/C) domain 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 3653..4052
FT /note="Adenylation 4"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 4251..4685
FT /note="Dual epimerase/condensation (E/C) domain 3"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 4727..5131
FT /note="Adenylation 5"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT REGION 5307..5532
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:33158886"
FT MOD_RES 932
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 2032
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3088
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 4165
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 5244
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 5532 AA; 608088 MW; 0AD204928473B053 CRC64;
MVDDDKHAKA SSQTSFKIDT GNAHIAQGTF ISVNAETGDI IDGLSISIGA IDAKEKVESV
VSISEIAAHE IVKTAKNAAR PHSPANRGDY PSVVATHGQS GERSYCASPM TRTVSVASSV
STLYPGTSEE ELSLDENNKI QADYWSKALA DVPAALELPT DRPRPLEPSI VGAEYPFQIG
TQLEQLLSSL GEEHDLNLAT TILVGWSIVL SRLSGQEDIL VGVCGVGEKG LPSSALPVRI
DLSGEPNTLQ LLGRVRDVLL AAGARGNLSQ KNIDLAVLSW QGKGVLSSQA AFYLHDGEAN
ATALDSAAVP FDIELHLYDT TEGASASLRY PPALFDTDTI KRYAGYLIAV LMNMIANGGQ
SVATIDIVSP AEKKLVLKTW NDSSAEYPSE RCVQQLFEDQ VEKSPDAIAI VHEGQPFTYL
ELDALADRIA HKLVHAGIKQ GDFVATLLLR SVELVAAQLA VLKIGAAYVP IDPKAPVDRQ
AFIVEDSASH LLITDVHAEV APALDLPLLR IDIAELQSRE EYSGAIAPTR SSQDTAYVMY
TSGSTGRPKG VLVPHKGIAR LVINNGFANI RSDDRIVFAA NPAFDASTFE VWAPLLNGGT
IVTVDADTVA DPYRFASVLD QHKITVLFMT PVMLNQHVST IGSSLAKLRY LISGGEQAST
ETYTALLRHQ GPVRLLNAYG PTEVTMLGTT YEARGGFEKL EKIPIGKPIG NTYTYVLDKH
GKPVPMGAVG ELYIGGDGVA NGYLNRPDLT AERFIPDPFS STHGARLYRS GDLVRHLPDG
NIVFMGRNDD QVKIRGFRIE LGEIEARLVE HDLVRESVVL ALGEGSEKRL VAYVVAEPTE
GLAHALRSHI EERLPVYMIP AAFVRLDAIP VTANGKVDRR ALPEPQEDAF ARQAYEAPCG
ETEEAIAAIW SELLGVNQIS RHDSFFALGG HSLLVVKMLD RLHRLGLTVS VRVLFESPTL
SVLAQDLSKH QAMIIPPNLI TLETFKLTPE MLPLIDLKQD DIDRIISQVP GGIHNIQDVY
SLAPLQDGIL FHHLLATEGD PYLLISHHAF RDRVLVDRYL DAFQRVVDRH DILRTAFFWD
ALSTPAQVVL RSAPLSVTEH VLDPAAGPVA DQLSQRYNHS KYRMDLTQAP LLRFALAEDV
DGRWIMAQMM HHLIIDHAAI EVMNAEVEEM LEGREDTLST PPQFRDLVAQ VRAGPTLEEH
EHFFAEMLGD IEEPTLPFGL TEVHSNGDEV KEAHMTVPQD LNDRLRAQAK RLGVTLAALC
HTAWAQVLAR TSGQDHVVFG TLLVGGLQGE QGDQPGMGIS INTLPFRCDM DNRSVQECVS
QIHSRLAALV EHESASLALA QRCSGVPAGT SLFSSLMNYR HTLMQTTTND PSNLEFTGKE
ELVNHEGIEF LGRLERTNYP LAISVEDFGL ALGLTAQALQ PADPADVCRY MQQALFSLVL
ALEDAPDMPV SDLDVLPLDE RTTLLQLWNA TDSPFPENIC VHSLFEEQVK QTPMAIAVEH
GDQSLTYAEL NNRASHLAYQ LSAQGIIHGD RVATYLQRSF ELIAAQLAIL KVGAIYVPID
PKAPLDRQAY IVSDSDSRLV ITDENTDVPV AIGAPLFRLT SFHDEKLNTD MDASWRAYSG
LNSLKNDIAR SSLETAYIMY TSGSTGLPKG VMVAHRGIAR LVFNNGFAVI TPEDRVAFSM
NPTFDPSTFE VWAPLLHGAR SVIIDYETFT DAHLLAKALN RHNITFLTLS TALFHQIVYV
IGPVLSNLRY IMAGGEQPST EAFSTLFEHG GRVQMINAYG PTEATVVTTA YVATGSTEAM
DRLPIGRPIS NTQLYVLDKH RNPVPIGVVG ELYVGGPGVA NGYLNRPDLT EQRFVVDPFS
QAQGARLYKT GDLVRYLRDG NLVFMGRNDD QVKIRGFRIE LGEIEERLAE HPQVREVAVL
ALGESGSKRL VAYVVADAAE RLAQTLREHL ATSLPEYMIP SAVVRLDAFP LTNNGKVDRR
ALPVPDLSAF ITEDYVPPEG VIETTVAAIW SEVLKIDKVG RYDNFFTLGG HSLLAVRLVN
RISTLGAQVP VATLFTSPTL SSFAEAVNTL LQHDDQTLSI IRPVSRDAPL ELSFAQQRLW
FLAQMPGVSD TYHMPLAMRL KGSVDRSALR KTLNTLFSRH EALRTVFVAV NGQPQVHLLA
ADTEIEMPFD DLTTENDKDD KLKELTSKAF DAPFDLEKGP LMRARLAQIS NDEFVFMLTQ
HHIVSDGWSM GVLIRELSEL YSSFCVGGYD PLEPLDVQYP DYAAWQRRWL AGDRLEEQGS
YWRKNLAGSP VSIDLPTDRP RPAEQSFAGA VVPIRINAQL SQALKTLSHK QGTTTFMTAL
AAWSAVLSRL SGQDDVVIGT PSANRNHQQV ERLIGFFVNT LALRIDLSGE PSVEQLLERV
RESTVAAQAH QDLPFEQVVE IAQPPRRMDQ TPLFQVMFSW QNDDIDSIRM PHLEATLEEV
HYEIAKFDLE LELYEHNDEI HGSLMYSTAL FDASTIERQV GYLEAMLRAM TTDVSQPIEA
VDLLGAPEKE LLLKTWNQTD KPFPDDRCIH ELFEDQAKRS PDAIAVEHDE RTVSFRDLSA
LVNNLTHQLI QAGVKAGDFV PTLLSRSIDL VAAQIAILKA GAAYVPIDPK APADRQAYIA
ADSGARLLVT DEHATVTPLI QTPIFRLRKD LAAETEKQEL ALPAVAARDT AYVMYTSGST
GLPKGVMVSH RAIARLIFND GYVDMNSDGC MIYGSNPAFD ASTAEVWAPL LHGGRMVIVD
VETYTDPHRL AAVLDRSKAT VLSLTPSLMN HYVSIIGPSL SRLQYLVSGG EQGNLPVYAA
LLRLGGPVRL VNAYGPTEVT TDTTTYEANA DTINQLERLP IGRPICNTQA YVLDKYHNPV
PLGAVGELYI GGPGVATGYL NRPDLTAERF LIDPFSQTEG ARMYKSGDLV RYLPDSNLIF
MGRNDDQVKI RGFRVELGEI EERLVEHQSV REAVVLAVGE GSDKRLIAYV ISEPLHQLPH
VMREYLAASL PEYMIPAAFV RLESMPLTNN GKVDRRALPE PGSDAFVSRE YEEPQGEIET
TLAATWSELL KIDKIGRQDN FFMLGGHSLL AVQMIEQLRR MGLVMSVRAL FETPVLNVLA
TSICRESVVR EAPTTPANLI THATTKVTPD LLPLIDLQQD DIDRIIDQVP GGVANIQDIY
SLSPLQDGIL FHHMMATEGD PYLLTICTAF RNRDLLDRYL GAIQRIVDRH DILRTAIVWR
NMTTPAQVVL RNAAISVTEL TLDPADGPII EQLKQRYDDR KYRIELDVAP LNRYAFAQDV
DGRWIMVQML HHIIGDHSTM EIMEEEIEKI LAGHGDTLAE PQPFRNLIAQ VRMGKTVEEH
EQFFSKMLSD FDTPALPYGL SDVHREGADV KEHHLMLPQD LNDRLRTQAK RLGVSLASLC
HLAWAQVIAA TSGQQHVVFG TVLFGRMQGG SGADRAMGLF INTLPLRVDV ENATVIESVR
RVQTDLATLL EHEHASLALA QRCSSIPSGS PLFSAILNYR HNVVLPEQAE LNTGIELLDG
QERSSYPFVM SVEDFGDSLG VTAQIVEPHD SLGICGYMQQ ALLSIVHALE QSPESPVHAL
SILSSEERDL MVRVWNNTHA EFPADRRIHQ LFEDHAALSP EAIALVLDDQ SLTYDELNVR
ANVLAHRLIE QDVRHGDYVA LLLHRSFDLV AAQLAVLKVG AAYVPIDSKA PVDRQAYIVK
DSASRLLITD AQMSVPSALE VQLLRLDSTD SVLAESDNIA LAGSSQDTAY AMYTSGSTGL
PKGVMVPHRA ISRLVINCGY ANIGPEDRVA FAANPAFDAS TFELWAPLLN GGCAVIIDAD
TFTDSHLLAK ALERHRINTL WLTMALFNQY VLSIGPALAK LKYLLCGGEQ GNLETFAALL
KHGGPENLIN GYGPTETTTF ATTFNASGMD DHFDRLPIGR PIGNTQVYVL DKHCNLVPLG
ATGELYIGGA GVATGYLAQP NLTAERFLPD PFSEDENARM YKTGDLVRYL PDGNLVFMGR
NDEQVKIRGF RIELGEIEAR LVEHELVKEA VVLALGEGGD KRLVAYVAAD PNEQLALTLR
THLATNMPDY MVPAAFVRLD TLPVTNNGKV NRRALPKPDS SAFAAQGYEE PRGEVEKALA
TIWTQLLKME RVGRNDNFFM LGGHSLLAVQ MIEQLRRIGL SLSVRALFDT PVLSVLAASL
NTHHSAPKTP ANLITAATTA ITPDLLPLIN LTQGDIDRIV DQIPGGVANI QDIYSLSPLQ
DGILFHHMMA TEGDPYLLIA GFTFRTKELL DRYLVAVQQI VDRHDILRTA IVSQNMTVPA
QVVVRKAAIS YTELTLDPAD GPLSDQLMQL YDTRKYRIEL HNAPLVRFVY SKDVDGRYVM
VQLLHHIIGD HSTMEIMEEE IETILAGEED TLAAPQPFRN LIAQVRMGKT IQEHEQFFSK
MLSDIDTPAL PYGLSDVHRE GADVTETHLM LPQDLNDRLR SQAKRLGVSL ASLCHLAWAQ
VIAATSGQQH VVFGTVLFGR MQGGSGADRA MGLFINTLPL RVDVENATVL ESVRRVQTDL
ATLLEHEHAS LALAQRCSSI PSGSPLFSAI LNYRHYAAPP VETATDNGIV AIEGNERTNY
PFTLSVEDFV SAFGVTVQVV QPYDSLSICG YMQQALQSLA DALEHSPDAP IQGLKVLPAE
EQDLLVHSWN QTGAAFPADQ CVQHVFESQV IERPEAIAMV HGDQTLTYRE LNTRANSLAQ
RLVEAGVNPG DFVSTLLVRS FDLVTVQLAI VKAGAAYVPI DIKSPADRQA YIASDSGAKL
LVTDEHTVVH ESIEIPIFRL GQVETKDSSQ QDWPLSFREG GSSLDAAYVM YTSGSTGMPK
GVMIPHRGIT RLVINNGHAN YGPDDRVVFG ANPAFDASTM EVWAPLMNGG RLVIVDAGTY
TDPEKLACLL EQQAVTVLFL TTALLNHYVP IIGRSLSKLK YLISGGEQGS LHAYTSLLRL
GGRVRLINGY GPTESTTIAT TYEPTLHHLG QLENLPIGRP IANTQVYVLD KYFRPVPTGA
TGELYIGGAG LAIGYLNRPD LTAERFLPNP FSDCEGARMY RTGDLVKYLP DGNLVFMGRN
DEQVKIRGFR IELGEIEARL VEHELVKQAV VLALGNGGDK RLVAYVVADH SEELVHTLRA
HLTATMPEYM IPAALVRLDA LPVTNNGKVN RRALPEPEAS AFAVRSYEAP KGDVEIGLAE
IWAELLSLDR VGRHDNFFML GGHSLLAVRM SGSVRSRLGL DLKLHTLFAA PTITDLAQKL
LQEASSDDDE YSVIFPLKTT GTRPPLFCVH SGIGLSWPYI GLVKHLHPDQ PVYGIQARGL
DRKTKLATSV EEMTEDYIEQ IRRIQPHGPY HFLGWSFGGT VAHSMATELE KQGEQVPLLV
IMDSTADYSI VADVQIDDTE VGANLEHLIR FGGEFSAEDG GAMWERTKPI NDNSFVLAMK
FKPSVYSGDI LFFRATLQED ELTPMVDPLS WTPYLAGAIE VHDVECTHIE MDKPAPMTII
GQTVASKLER AL
