ID   CHSAD_CHOCO             Reviewed;        3912 AA.
AC   Q0VZ70;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2006, sequence version 1.
DT   03-AUG-2022, entry version 78.
DE   RecName: Full=Chondramide synthase cmdD {ECO:0000303|PubMed:16793524};
DE   Includes:
DE     RecName: Full=ATP-dependent phenylalanine adenylase;
DE              Short=PheA;
DE     AltName: Full=Phenylalanine activase;
DE   Includes:
DE     RecName: Full=ATP-dependent tyrosine adenylase;
DE              Short=TrpA;
DE     AltName: Full=Tyrosine activase;
GN   Name=cmdD {ECO:0000312|EMBL:CAJ46692.1};
OS   Chondromyces crocatus.
OC   Bacteria; Proteobacteria; Deltaproteobacteria; Myxococcales; Sorangiineae;
OC   Polyangiaceae; Chondromyces.
OX   NCBI_TaxID=52;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:CAJ46692.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DOMAIN.
RC   STRAIN=Cm c5 {ECO:0000269|PubMed:16793524};
RX   PubMed=16793524; DOI=10.1016/j.chembiol.2006.06.002;
RA   Rachid S., Krug D., Kunze B., Kochems I., Scharfe M., Zabriskie T.M.,
RA   Blocker H., Muller R.;
RT   "Molecular and biochemical studies of chondramide formation-highly
RT   cytotoxic natural products from Chondromyces crocatus Cm c5.";
RL   Chem. Biol. 13:667-681(2006).
RN   [2] {ECO:0000305}
RP   FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND DOMAIN.
RC   STRAIN=Cm c5 {ECO:0000269|PubMed:17545150};
RX   PubMed=17545150; DOI=10.1074/jbc.m703439200;
RA   Rachid S., Krug D., Weissman K.J., Muller R.;
RT   "Biosynthesis of (R)-beta-tyrosine and its incorporation into the highly
RT   cytotoxic chondramides produced by Chondromyces crocatus.";
RL   J. Biol. Chem. 282:21810-21817(2007).
CC   -!- FUNCTION: Involved in the synthesis of chondramides. Activates R-beta-
CC       tyrosine and probably phenylalanine. {ECO:0000269|PubMed:16793524,
CC       ECO:0000269|PubMed:17545150}.
CC   -!- COFACTOR:
CC       Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC         Evidence={ECO:0000250|UniProtKB:P0C061};
CC       Note=Binds 2 phosphopantetheines covalently.
CC       {ECO:0000250|UniProtKB:P0C061};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.2 mM for R-beta-tyrosine {ECO:0000269|PubMed:17545150};
CC   -!- DOMAIN: Two module-bearing peptide synthase. Each module incorporates
CC       one amino acid into the peptide product and can be further subdivided
CC       into domains responsible for substrate adenylation, condensation and
CC       epimerization (Probable). {ECO:0000269|PubMed:16793524,
CC       ECO:0000269|PubMed:17545150, ECO:0000305}.
CC   -!- MISCELLANEOUS: Chondramides are secondary metabolites with antifungal
CC       and cytotoxic activity. They are non-ribosomally produced depsipeptides
CC       consisting of a polyketide chain and 3 amino acids (alanine, N-
CC       methyltryptophan and beta-tyrosine or alpha-methoxy-beta-tyrosine).
CC   -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC       {ECO:0000255}.
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DR   EMBL; AM179409; CAJ46692.1; -; Genomic_DNA.
DR   SMR; Q0VZ70; -.
DR   STRING; 52.CMC5_047510; -.
DR   PRIDE; Q0VZ70; -.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0008168; F:methyltransferase activity; IEA:InterPro.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0016772; F:transferase activity, transferring phosphorus-containing groups; IEA:InterPro.
DR   GO; GO:0043042; P:amino acid adenylylation by nonribosomal peptide synthase; IDA:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:InterPro.
DR   GO; GO:0009403; P:toxin biosynthetic process; IDA:UniProtKB.
DR   Gene3D; 1.10.1200.10; -; 2.
DR   Gene3D; 3.30.300.30; -; 3.
DR   Gene3D; 3.30.559.10; -; 3.
DR   Gene3D; 3.40.50.150; -; 1.
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; IPR000253; FHA_dom.
DR   InterPro; IPR013216; Methyltransf_11.
DR   InterPro; IPR010060; NRPS_synth.
DR   InterPro; IPR008279; PEP-util_enz_mobile_dom.
DR   InterPro; IPR036637; Phosphohistidine_dom_sf.
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; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR001031; Thioesterase.
DR   Pfam; PF00501; AMP-binding; 2.
DR   Pfam; PF13193; AMP-binding_C; 1.
DR   Pfam; PF00668; Condensation; 3.
DR   Pfam; PF08241; Methyltransf_11; 1.
DR   Pfam; PF00391; PEP-utilizers; 1.
DR   Pfam; PF00550; PP-binding; 2.
DR   Pfam; PF00975; Thioesterase; 1.
DR   SMART; SM00823; PKS_PP; 2.
DR   SMART; SM00824; PKS_TE; 1.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   SUPFAM; SSF52009; SSF52009; 1.
DR   SUPFAM; SSF53335; SSF53335; 1.
DR   SUPFAM; SSF53474; SSF53474; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR   TIGRFAMs; TIGR01720; NRPS-para261; 1.
DR   PROSITE; PS00455; AMP_BINDING; 2.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 2.
PE   1: Evidence at protein level;
KW   Ligase; Multifunctional enzyme; Phosphopantetheine; Phosphoprotein; Repeat.
FT   CHAIN           1..3912
FT                   /note="Chondramide synthase cmdD"
FT                   /id="PRO_0000407279"
FT   DOMAIN          1411..1485
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          2989..3064
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          1995..2030
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         1446
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000250|UniProtKB:P0C061,
FT                   ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         3024
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000250|UniProtKB:P0C061,
FT                   ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   3912 AA;  432413 MW;  C1DBA62EB27C2B9B CRC64;
     MLREGQGTVA HAPPRPLPHA DVLPVSQAQR RLWFLCQLDG ASVAYNMPFV TALDGHLDAR
     ALQRALDEII RRHESLRTTF RLQAEGPVQV IHPPAPLDLP LHDLRSLDEP ARAAEIQRRI
     DRAAHQPFDI ERGPLLRAQL LRQSETRHVL CLVIHHIVAD GWSIGVFVRE FEALYGAFSA
     SRPSPLTEPP LQYADFSRWQ EERFPPSAVE RHLTYWKQKL SDVQPLQLPA DHPRPAVESF
     RGDHTIFRLD RGLTRGLHEL AQCEGVTLFI TLLSAFNVLL GRYSGQDDLA IASGTANRKH
     AELEGLIGFF VNTVVIRTDL SGNPTFRTVL SRVLASVMEA TEHEDLPFER VVEELKPERT
     ASHNPLAQVA LTLQSFASNR LTLPGLTTSP CDFRFRTSKL DLMLLVTEVD GELEVVVEYN
     TDLFEDATIA RMSAHLRTVM AAMVADPGAR IGDISLLTTE ERHRLLVDWN DTALACPEAE
     GVHHAFEQNA ARQPDAIAVV FDGDPISRIT YGALNERANQ LAHHLIQQGV GPDVVVGIHV
     ERSITMIVAL LAVLKAGGAY LPLDPTYPQQ RLAFILADAG AQVILTQEKW FDDLPPHTAR
     VLDLDAIAPQ LDANATSNPP LRATADHLAY IIYTSGSTGN PKGVLIPRRD TWSVARALAE
     TYALTPESRV LQFASLNFDG SVVEITMTLF SGAALHVAPQ EKLLPGAPLN AFLQRHAITH
     VQLAPSLLAR LPPEGLEHVR TIMVAGEASS VGTVRGWLPG RRILNGYGPT ETTVGAAMIA
     FTEADDAYLA KLDALPIGRP FYNKRVYLLD ARLQPVPVGV PGEIYVASPG LARGYINRPA
     ATAEKFLPNP FSETPGERIY RTGDLARYLP DGNLVFLGRV DNQVKLRGLR IELEEIESAL
     KSHPHVGDAA VIVHEAPADQ ATSERDGKRL VAYVVPRRGW EPEGAQSDHI ASWQTLHEQL
     LDESQAPEDW SFNITGWKSS YTGEALPAAE MRLWVESTVE RILAHGPKDV LEIGTGTGLL
     LARIAPRVRA YLATDFSLEA IRYLETCKAR APELSNVTLL QRMADDFTGF SAGQFDTIVL
     NSVVQYFPTL DYLSAVIEGA LRVLKPGGTL FLGDIRNLAL LDAFHASVQT AKASGTLSRD
     ELRYRVQQGV MNENELVIDP RFFTALSRKF PQITHVEVTP KRGLHRNELT LFRYDVALQV
     GGTPKGAPTI TWFDWREEGL TSDSLPPWLS DTLATSPDAG VGLRRVPNAR LQPDLAILSW
     LATRAEASLD AWRARQHDVP EGCAPEALWA LETTWPGRVH LSWAAGHPDG SFDLVVTPPQ
     AERRAPWSPA VDLTDEQLSA YVNHPLQAKV VRETLGQELR RYLQDKLPAY MVPTVLIPLP
     ALPLTSNGKL DRRALPAPDI ERRSRASTYV APRNAREETL VAIWSKVLGV DPIGVEDNFF
     ELGGDSILSI QIVGQAKQAG FSLTSRQMFE HQTIAALAEV ASASKSIQAE QGLVEGSIPL
     TPIQRWFFET HQETPDHFNQ AILLKVSADV SASRLEQAFH HLFTHHDALR MRFSRTADGF
     EQVNLGPIEG VTVDVIDLAH LPAAEQTRAL TEAATSLQQR LSITSGPLSR IALIHLGAEQ
     PARLLWILHH LVVDGVSWRI LLDDLVTVLR QLEAGQPARF PPKTTSFKEW SERLHATAQQ
     EQANTASSRA ERDAWRSVPV PALPLDHPQG TNRKASAAQV QVALSVADTH ALLHDAPRAY
     GTQVNDLLLT ALALAFNAWT GDATLALDLE GHGREEDLVG ADLSRTVGWF TTMHPVALRL
     PGRELSLALR AVKEQLRAQP GRGIAYGLFR YASGEGSLAS WPAPQVNFNY LGQLDAMTDT
     APLLGFAPEE IGPSDGPTGD RTHLFQVNGM VKDGSLQFTW TYSRELHRPE TVQKLAHDFA
     ETARRLTQHC LAHESHPTPG DFPAVTLSQN QLDVVLDALG ADRDNVAAIY PLTSLQEGLL
     FHSLSAVPAP VPALADEDDE EDDELDEEFD AEVDEEDEDE EEEEDDDGEN VYVTQLVFRI
     QGPLDAEKFR TAWQETVQRH PLLRSRFVWE GCERPLQVVL RSADLRWEED ELEEDSWSSP
     LRVHARREQQ AGMLLDEAPL FRLNLLRAED TEHHLIWTSH HILLDGWSGP LILKDVFASY
     DAQLLGESRT AADPPPYEAY VAWLKRQDGT ASERFWRENL RGFSAPTPLV VDNEEPTGKQ
     KHLHHRCKLS AETSQALKAL AESFRVTLST VYQAAWALLL HRYSGMSDVL FGVTVSGREA
     DVPGIEEMVG LFIRTVPLRL HVDESQTLGA WLKEVQARQI EQREHQYVSL VDIQRWSDVP
     GGTQLFDSMF VFENYPLDSA LLEQSGLRLT VSTMASPTHY PLVIAVVPGR TVETLFDHDT
     SRLSKHTVER LAAHWVELLT GMARRPDARI HTLPHLTSAE REKLLVTWNA RPYVDEQRKY
     RGEEEPFGEE LAAESTFLDL FQHHVAQTPD ALALVGPSLQ STDERPVSRT YRALSARVHL
     LARHLRGLGV GPEVTVGVCL DRSIELVIGM LAIFEAGGVY LPLDPSQPLE RLAYLVSDAR
     PEVVLTQQRW NDRLPEQATR RVALDTAWAE IEAQPEVSHQ HRTAGDNLAY VLYTSGSTGT
     PKGVQVTVDN LSRLTPALIT AFDVTPRSRV LQYSSLSFDG SISEVAMALG AGAALHLAPA
     HELVPGPPLQ KLLATRAITH VTLLPAALRW LSPRGLPALD VLIVTGEACP ASLVRTWASG
     RRFVNAYGPT EITVAATAME CPVTMFQETE QPPPIGCPLQ STEIYILDAH LRPVPVGVPG
     DLYIGGAKLT RGYIHRPALT AERYIPHPFS DRPGARLYVT GDIARYQLDG TIDFLGRRDN
     QVKVRGYRIE LGEVEAALND HPGVREAVVV AQKDGAGDNR LVAYWAAKST PPTTTEALRD
     ALSKRLAAYM IPSVFVRMDA LPLNATGKID RQGLPPVDDT MLDREQFVAP RTATEETLTA
     IWSSTLGVAR VGIRDDFFKL GGHSLLALNI TTQIQKRFGH VITVDSIFRA PTIAVLARVI
     DEALAPTGAR RALSLVVPLR ERGTKVPLFF AAGMGMHAHY LRPLAEHLGE DQPFYALQSP
     AQGGEITDMA TLVDTLIGAI QQIQPSGPYH LGGHSAGARI AFAVALELQR RGAEVPLVSI
     VDMRPPGRGA TSDESAEWTQ IGGLIGYVTM IKQAIGEGVL FVTPEELRKL DEAAAWQRTL
     DAFIAARWMP KDADVEQLQH LCAMNQNVVR VVRDHVPTDT HQGKLLVFSA AFAMRNGRQV
     STEGWQAFCA NPVTTHEVPG DHMTMLREPD VRGLAIKLRR EIDELALERT DEAPGLPTPP
     EFPVVWEHPE DARMLWVHDV THCREQMTPL DFCLRQQAMV EGSNLANLAY GVPFTGEIRL
     INTYVYQKII PTTASPTELA AAMKRAEASV AALLPDLGRW WTETLLPEIE AHLEALDPEN
     NYDFVHRHTL VEALAEAHRR TARLWEIHFR LLQPVMLAIS RFVDLCKDLS TDDDPIDPYA
     LLVGFPNKTT EGNRALWSLS RLALETPEVA SILTSNEASR VSWKLRSTRG GRAFVAQLDA
     YLATYGQRND STYLDAPTWE EDPTPVIRNL QAYMTQPERD LDAELNALSE QRTQRLDALR
     ARLRHYPRAV VDEFEQALTA AQTATVLSED HNYWIDYKIT HRLRHLCLYL GEQLKDWELL
     GDCEEIFYLS MDDVSRAAVE TKRGGPFSAN QRFYHLACAR KDEAKRFHGV QPPRFLGTPS
     PLPALHDALS LASARFTGVA PSPSNDEKEI VGLSGAKGKA RGKARVARNL ADVPTLEPGE
     ILVAMAMLPA WTPLFATVAA IVTDSGGMLS HAAVVAREYG IPAVVGTQVG TQRIRDGQLV
     EVDGERGVVT LL