ID   CICB_EMENI              Reviewed;        1039 AA.
AC   A0A1U8QW91; C8V0E0; Q5AZ36;
DT   07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2017, sequence version 1.
DT   03-AUG-2022, entry version 20.
DE   RecName: Full=Adenylate-forming reductase cicB {ECO:0000250|UniProtKB:Q0CRQ4};
DE            EC=1.2.1.- {ECO:0000250|UniProtKB:Q0CRQ4};
DE   AltName: Full=Cichorine biosynthesis cluster protein B {ECO:0000303|PubMed:24244835};
DE   AltName: Full=Nonribosomal peptide synthase-like protein cicB {ECO:0000250|UniProtKB:Q0CRQ4};
DE            Short=NRPS-like protein cicB {ECO:0000250|UniProtKB:Q0CRQ4};
GN   Name=cicB {ECO:0000303|PubMed:24244835}; ORFNames=AN6444, ANIA_06444;
OS   Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS   M139) (Aspergillus nidulans).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Nidulantes.
OX   NCBI_TaxID=227321;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=16372000; DOI=10.1038/nature04341;
RA   Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA   Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA   Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA   Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA   Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA   Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA   Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA   Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA   Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT   "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT   fumigatus and A. oryzae.";
RL   Nature 438:1105-1115(2005).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX   PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA   Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA   Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA   Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA   Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA   Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA   Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA   Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA   van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA   Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA   Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA   Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA   Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA   Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA   van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA   Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA   Oliver S.G., Turner G.;
RT   "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT   effort.";
RL   Fungal Genet. Biol. 46:S2-13(2009).
RN   [3]
RP   FUNCTION.
RX   PubMed=22510154; DOI=10.1021/ja3016395;
RA   Ahuja M., Chiang Y.M., Chang S.L., Praseuth M.B., Entwistle R.,
RA   Sanchez J.F., Lo H.C., Yeh H.H., Oakley B.R., Wang C.C.;
RT   "Illuminating the diversity of aromatic polyketide synthases in Aspergillus
RT   nidulans.";
RL   J. Am. Chem. Soc. 134:8212-8221(2012).
RN   [4]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX   PubMed=24244835; DOI=10.1039/c2md20055d;
RA   Sanchez J.F., Entwistle R., Corcoran D., Oakley B.R., Wang C.C.;
RT   "Identification and molecular genetic analysis of the cichorine gene
RT   cluster in Aspergillus nidulans.";
RL   Med. Chem. Commun. 3:0-0(2012).
RN   [5]
RP   BIOTECHNOLOGY.
RX   PubMed=30708999; DOI=10.3390/molecules24030515;
RA   Liao L., Zhang X., Lou Y., Zhou C., Yuan Q., Gao J.;
RT   "Discovery of three new phytotoxins from the fungus Aspergillus nidulans by
RT   pathway inactivation.";
RL   Molecules 24:0-0(2019).
CC   -!- FUNCTION: Nonribosomal peptide synthase-like protein; part of the gene
CC       cluster that mediates the biosynthesis of cichorine, a phytotoxin
CC       active against knapweed, corn, and soybeans (PubMed:24244835). The
CC       first step in the pathway is performed by the non-reducing polyketide
CC       synthase pkbA that condenses one acetyl-CoA starter unit with 3
CC       malonyl-CoA units (PubMed:22510154). PkbA also catalyzes one
CC       methylation step to produce 3-methylorsellinate (PubMed:22510154). The
CC       nonribosomal peptide synthase-like protein cicB, the cytochrome P450
CC       monooxygenase cicH and the O-methyltransferase cicE are involved in the
CC       conversion of 3-methylorsellinate into nidulol (PubMed:24244835). CicB
CC       converts 3-methylorsellinate to a yet unidentified intermediate, cicH
CC       may play a ring-closing role for cichorine and cicE is plausibly
CC       responsible for the methylation of one of the phenol groups (Probable).
CC       The oxidoreductase cicC acts downstream with still unidentified enzymes
CC       to further convert nidulol into cichorine (PubMed:24244835).
CC       {ECO:0000269|PubMed:22510154, ECO:0000269|PubMed:24244835,
CC       ECO:0000305|PubMed:24244835}.
CC   -!- PATHWAY: Phytotoxin biosynthesis. {ECO:0000269|PubMed:24244835}.
CC   -!- DOMAIN: Contains three distinct domains: an adenylation (A) domain that
CC       activates the substrate amino acid which is subsequently covalently
CC       linked as a thioester (aminoacyl-S-PCP) to the 4'-phosphopantetheine
CC       prosthetic group of the second domain, the peptidyl carrier protein
CC       (PCP) domain, as well as a reductase (R) release domain.
CC       {ECO:0000250|UniProtKB:Q0CRQ4}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of cichorine and leads
CC       to the accumulation of 3-methylorsellinic acid.
CC       {ECO:0000269|PubMed:24244835}.
CC   -!- BIOTECHNOLOGY: Cichorine and its derivatives are promising in the
CC       course of developing novel herbicides. {ECO:0000269|PubMed:30708999}.
CC   -!- SIMILARITY: Belongs to the adenylate-forming reductase family.
CC       {ECO:0000305}.
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DR   EMBL; BN001301; CBF69459.1; -; Genomic_DNA.
DR   EMBL; AACD01000108; EAA58466.1; -; Genomic_DNA.
DR   RefSeq; XP_664048.1; XM_658956.1.
DR   AlphaFoldDB; A0A1U8QW91; -.
DR   SMR; A0A1U8QW91; -.
DR   STRING; 162425.CADANIAP00006531; -.
DR   EnsemblFungi; CBF69459; CBF69459; ANIA_06444.
DR   EnsemblFungi; EAA58466; EAA58466; AN6444.2.
DR   GeneID; 2871339; -.
DR   KEGG; ani:AN6444.2; -.
DR   VEuPathDB; FungiDB:AN6444; -.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_002220_2_1_1; -.
DR   OMA; YDWKYFR; -.
DR   OrthoDB; 229565at2759; -.
DR   Proteomes; UP000000560; Chromosome I.
DR   Proteomes; UP000005890; Unassembled WGS sequence.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0062032; P:cichorine biosynthetic process; IMP:GO_Central.
DR   Gene3D; 3.40.50.12780; -; 1.
DR   InterPro; IPR020845; AMP-binding_CS.
DR   InterPro; IPR000873; AMP-dep_Synth/Lig.
DR   InterPro; IPR042099; ANL_N_sf.
DR   InterPro; IPR013120; Far_NAD-bd.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF07993; NAD_binding_4; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; NADP; Nucleotide-binding; Oxidoreductase; Phosphopantetheine;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..1039
FT                   /note="Adenylate-forming reductase cicB"
FT                   /id="PRO_0000450884"
FT   DOMAIN          567..649
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          91..366
FT                   /note="Adenylation (A) domain"
FT                   /evidence="ECO:0000250|UniProtKB:Q0CRQ4, ECO:0000255"
FT   REGION          685..910
FT                   /note="Reductase (R) domain"
FT                   /evidence="ECO:0000250|UniProtKB:Q0CRQ4, ECO:0000255"
FT   BINDING         256
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q6RKB1"
FT   BINDING         350..351
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q6RKB1"
FT   BINDING         355
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q6RKB1"
FT   BINDING         429..432
FT                   /ligand="AMP"
FT                   /ligand_id="ChEBI:CHEBI:456215"
FT                   /evidence="ECO:0000250|UniProtKB:Q6RKB1"
FT   BINDING         689..692
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6RKB1"
FT   BINDING         777..779
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6RKB1"
FT   BINDING         855
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6RKB1"
FT   BINDING         859
FT                   /ligand="NADP(+)"
FT                   /ligand_id="ChEBI:CHEBI:58349"
FT                   /evidence="ECO:0000250|UniProtKB:Q6RKB1"
FT   MOD_RES         600
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1039 AA;  114875 MW;  1C3C0C9C7B13F571 CRC64;
     MARNQQLRPF KRPAIRLYPA VNETELIRTL PEVVEFNAQA NPDHVFCLQA KKSPNKSILS
     LVSVTNRQLK QAISQCVGWL KSNLKLQLPS LLHGSVEKGA PVALLMESDI GLFIYEIALI
     GLGVPVLLLS ARLSAPAINS LLQRTSAAAI IVSGRLEATA REAAETLPAA VFSPLPFEAF
     LSTNEGLPDN DSICHPYHYI DESDRNVLIL HSSGTTGLPK PIYVSHRHLL SFVNCHRLDL
     ESEAQGVNVS TLPLYHGFGL VAPALAMGVG KTVCFPPGST VPSAGATLDL LRISNAASFM
     TVPSILEDIA FLGDEGIQAL AGLDYVTFGG GILKPSVGEE LAVHGVKLLN HYGTTESGPL
     APIFVPQDDY NWRFFRLRDD LRLQLDEIAP NGNERRFKLT TFPFGLEQPF EIQDQLVCNP
     DYPGSDFNAV GRNDDTIVLA TGEKVQPQIL ESILCESSLV KSAIAFGEHQ FEIGVLVQLA
     ADVPPKNYSK LREQLWPLVA RANESMDGHA RIQSSEAVLL LPSTVTIPRT DKGSIARKDV
     YKMFEADIAG VYRKLESAGP VLCLDMETLE EDLKLLISRC TDWPPDWAVT DDLFERGMNS
     LQAIRVQRAL VAAVTRSLRG VCQPERIGRD FVYIHPSVRA MADFFREPVN GLQLPNGFST
     RGWAPDQLVQ RFALTSKDGR ATVLLTGATG SLGSHCLLSL IQSPNIKRVI CLVRPEDSFT
     DPRLRLQKSL ESKKLHLSST QWSMVDVLGC HTASQYLGLT REQYTILQES VTYILHAAWP
     MDFHWKLPSF QSQFQSLHNL LALARDIHNR RPSIKPRLTF ISSIATVGQY ARVHGVRMVP
     ETSVDSVECL NPIGYAEAKL VCERMLEHAR LHYPHEMTVS YVRMGQIAGS STTGFWNINE
     HIPALTLSWI PVDVAAQSIT ELLLSPAPAE LIYHIENPIR QSWHDMLQTI AAVLHLSASD
     ALPWNEWQEQ VAAAGDTDNP AKKLQDFFAN DFIRMGCGEV VLGTDKARKA SATLRRVDAV
     SEGCVRGYLQ YWKEIGWLK