FUM14_GIBM7
ID FUM14_GIBM7 Reviewed; 548 AA.
AC Q8J2Q6; W7LKY1;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 2.
DT 25-MAY-2022, entry version 82.
DE RecName: Full=Nonribosomal peptide synthetase 8 {ECO:0000303|PubMed:12620260};
DE EC=6.3.2.- {ECO:0000269|PubMed:16489749};
DE AltName: Full=Fumonisin biosynthesis cluster protein 14 {ECO:0000303|PubMed:12620260};
GN Name=FUM14 {ECO:0000303|PubMed:12620260}; ORFNames=FVEG_00325;
OS Gibberella moniliformis (strain M3125 / FGSC 7600) (Maize ear and stalk rot
OS fungus) (Fusarium verticillioides).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC Fusarium fujikuroi species complex.
OX NCBI_TaxID=334819;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PATHWAY.
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=12620260; DOI=10.1016/s1087-1845(02)00525-x;
RA Proctor R.H., Brown D.W., Plattner R.D., Desjardins A.E.;
RT "Co-expression of 15 contiguous genes delineates a fumonisin biosynthetic
RT gene cluster in Gibberella moniliformis.";
RL Fungal Genet. Biol. 38:237-249(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=20237561; DOI=10.1038/nature08850;
RA Ma L.-J., van der Does H.C., Borkovich K.A., Coleman J.J., Daboussi M.-J.,
RA Di Pietro A., Dufresne M., Freitag M., Grabherr M., Henrissat B.,
RA Houterman P.M., Kang S., Shim W.-B., Woloshuk C., Xie X., Xu J.-R.,
RA Antoniw J., Baker S.E., Bluhm B.H., Breakspear A., Brown D.W.,
RA Butchko R.A.E., Chapman S., Coulson R., Coutinho P.M., Danchin E.G.J.,
RA Diener A., Gale L.R., Gardiner D.M., Goff S., Hammond-Kosack K.E.,
RA Hilburn K., Hua-Van A., Jonkers W., Kazan K., Kodira C.D., Koehrsen M.,
RA Kumar L., Lee Y.-H., Li L., Manners J.M., Miranda-Saavedra D.,
RA Mukherjee M., Park G., Park J., Park S.-Y., Proctor R.H., Regev A.,
RA Ruiz-Roldan M.C., Sain D., Sakthikumar S., Sykes S., Schwartz D.C.,
RA Turgeon B.G., Wapinski I., Yoder O., Young S., Zeng Q., Zhou S.,
RA Galagan J., Cuomo C.A., Kistler H.C., Rep M.;
RT "Comparative genomics reveals mobile pathogenicity chromosomes in
RT Fusarium.";
RL Nature 464:367-373(2010).
RN [3]
RP FUNCTION.
RC STRAIN=M3125 / FGSC 7600;
RX PubMed=10413619; DOI=10.1006/fgbi.1999.1141;
RA Proctor R.H., Desjardins A.E., Plattner R.D., Hohn T.M.;
RT "A polyketide synthase gene required for biosynthesis of fumonisin
RT mycotoxins in Gibberella fujikuroi mating population A.";
RL Fungal Genet. Biol. 27:100-112(1999).
RN [4]
RP FUNCTION.
RX PubMed=14602658; DOI=10.1128/aem.69.11.6935-6937.2003;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "FUM9 is required for C-5 hydroxylation of fumonisins and complements the
RT meitotically defined Fum3 locus in Gibberella moniliformis.";
RL Appl. Environ. Microbiol. 69:6935-6937(2003).
RN [5]
RP FUNCTION.
RX PubMed=12720383; DOI=10.1021/jf0262007;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "FUM13 encodes a short chain dehydrogenase/reductase required for C-3
RT carbonyl reduction during fumonisin biosynthesis in Gibberella
RT moniliformis.";
RL J. Agric. Food Chem. 51:3000-3006(2003).
RN [6]
RP FUNCTION.
RX PubMed=15066782; DOI=10.1128/aem.70.4.1931-1934.2004;
RA Ding Y., Bojja R.S., Du L.;
RT "Fum3p, a 2-ketoglutarate-dependent dioxygenase required for C-5
RT hydroxylation of fumonisins in Fusarium verticillioides.";
RL Appl. Environ. Microbiol. 70:1931-1934(2004).
RN [7]
RP FUNCTION.
RX PubMed=15137825; DOI=10.1021/jf035429z;
RA Bojja R.S., Cerny R.L., Proctor R.H., Du L.;
RT "Determining the biosynthetic sequence in the early steps of the fumonisin
RT pathway by use of three gene-disruption mutants of Fusarium
RT verticillioides.";
RL J. Agric. Food Chem. 52:2855-2860(2004).
RN [8]
RP FUNCTION.
RX PubMed=15969533; DOI=10.1021/jf050062e;
RA Yi H., Bojja R.S., Fu J., Du L.;
RT "Direct evidence for the function of FUM13 in 3-ketoreduction of mycotoxin
RT fumonisins in Fusarium verticillioides.";
RL J. Agric. Food Chem. 53:5456-5460(2005).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, DOMAIN, AND PATHWAY.
RX PubMed=16489749; DOI=10.1021/bi052085s;
RA Zaleta-Rivera K., Xu C., Yu F., Butchko R.A., Proctor R.H.,
RA Hidalgo-Lara M.E., Raza A., Dussault P.H., Du L.;
RT "A bidomain nonribosomal peptide synthetase encoded by FUM14 catalyzes the
RT formation of tricarballylic esters in the biosynthesis of fumonisins.";
RL Biochemistry 45:2561-2569(2006).
RN [10]
RP FUNCTION.
RX PubMed=16536629; DOI=10.1021/jf0527706;
RA Proctor R.H., Plattner R.D., Desjardins A.E., Busman M., Butchko R.A.;
RT "Fumonisin production in the maize pathogen Fusarium verticillioides:
RT genetic basis of naturally occurring chemical variation.";
RL J. Agric. Food Chem. 54:2424-2430(2006).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=17147424; DOI=10.1021/jf0617869;
RA Butchko R.A., Plattner R.D., Proctor R.H.;
RT "Deletion analysis of FUM genes involved in tricarballylic ester formation
RT during fumonisin biosynthesis.";
RL J. Agric. Food Chem. 54:9398-9404(2006).
CC -!- FUNCTION: Nonribosomal peptide synthetase; part of the gene cluster
CC that mediates the biosynthesis of fumonisins B1 (FB1), B2 (FB2), B3
CC (FB3), and B4 (FB4), which are carcinogenic mycotoxins
CC (PubMed:12620260, PubMed:16489749, PubMed:17147424). On the basis of
CC the chemical structures of fumonisins and precursor feeding studies,
CC fumonisin biosynthesis is predicted to include at least five groups of
CC biochemical reactions: synthesis of a linear polyketide with a single
CC terminal carbonyl function and methyl groups at C-10 and C-14;
CC condensation of the polyketide with alanine; reduction of the
CC polyketide carbonyl to a hydroxyl; hydroxylation of 2-4 polyketide
CC carbons; and esterification of six-carbon tricarboxylic acids to two of
CC the hydroxyls (PubMed:12620260). The biosynthesis starts with the
CC polyketide synthase FUM1-catalyzed carbon chain assembly from one
CC molecule of acetyl CoA, eight molecules of malonyl CoA, and two
CC molecules of methionine (PubMed:10413619). The C-18 polyketide chain is
CC released from the enzyme by a nucleophilic attack of a carbanion, which
CC is derived from R-carbon of alanine by decarboxylation, on the carbonyl
CC carbon of polyketide acyl chain (PubMed:15137825, PubMed:12720383).
CC This step is catalyzed by a pyridoxal 5'-phosphate-dependent aminoacyl
CC transferase FUM8 (PubMed:15137825, PubMed:12720383). The resultant 3-
CC keto intermediate 2-amino-3-oxo-12,16-dimethylicosane is then
CC stereospecifically reduced to the 3-hydroxyl product 2-amino-3-hydroxy-
CC 12,16-dimethylicosane by reductase FUM13 (PubMed:12720383,
CC PubMed:15137825). Subsequent oxidations at C-5, C-10, C-14 and C-15
CC followed by tricarballylic esterification of the hydroxyl groups on C-
CC 14 and C-15 furnish the biosynthesis of fumonisins (PubMed:15066782,
CC PubMed:15137825, PubMed:16489749). The C-10 hydroxylation is performed
CC by the cytochrome P450 monooxygenase FUM2 and occurs early in the
CC biosynthesis (PubMed:16536629). The C-5 hydroxylation is performed by
CC the dioxygenase FUM3 and occurs late in the biosynthesis
CC (PubMed:20237561, PubMed:15066782, PubMed:15137825, PubMed:16536629).
CC Cytochrome P450 monooxygenases FUM6 and FUM15 may be responsible for
CC the two remaining hydroxylations at positions C-14 and C-15
CC (PubMed:12620260). The FUM11 tricarboxylate transporter makes a
CC tricarboxylic acid precursor available for fumonisin biosynthesis via
CC its export from the mitochondria (PubMed:12620260). If the precursor is
CC citrate, the FUM7 dehydrogenase could remove the C-3 hydroxyl of
CC citrate to form tricarballylic acid either before or after the CoA
CC activation by the FUM10 acyl-CoA synthetase and FUM14 catalyzed
CC esterification of CoA-activated tricarballylic acid to the C-14 and C-
CC 15 hydroxyls of the fumonisin backbone (PubMed:16489749,
CC PubMed:17147424). Alternatively, if the precursor is cis-aconitate,
CC FUM7 may function to reduce the double bond (PubMed:17147424). In this
CC alternate proposal, feeding studies with tetradehydro-fumonisin B1
CC suggests that FUM7 cannot function on the tricarballylic ester and must
CC therefore act before the FUM14-mediated esterification
CC (PubMed:17147424). {ECO:0000269|PubMed:10413619,
CC ECO:0000269|PubMed:12620260, ECO:0000269|PubMed:12720383,
CC ECO:0000269|PubMed:14602658, ECO:0000269|PubMed:15066782,
CC ECO:0000269|PubMed:15137825, ECO:0000269|PubMed:15969533,
CC ECO:0000269|PubMed:16489749, ECO:0000269|PubMed:16536629,
CC ECO:0000269|PubMed:17147424}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:12620260,
CC ECO:0000269|PubMed:16489749, ECO:0000269|PubMed:17147424}.
CC -!- DOMAIN: FUM14 encodes a nonribosomal peptide synthetasecontaining two
CC domains, a peptidyl carrier protein domain and a condensation domain
CC (PubMed:16489749). The condensation domain catalyzes a C-O bond (ester)
CC formation and can convert HFB1, a precursor of fumonisin B1 lacking the
CC tricarballylic ester, to fumonisin B1 (PubMed:16489749).
CC {ECO:0000269|PubMed:16489749}.
CC -!- DISRUPTION PHENOTYPE: Loses the ability to produce fumonisins, but
CC accumulates two new metabolites, HFB3 and HFB4, which are biosynthetic
CC precursors of fumonisins lacking the tricarballylic esters
CC (PubMed:16489749, PubMed:17147424). {ECO:0000269|PubMed:16489749,
CC ECO:0000269|PubMed:17147424}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EWG36205.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF155773; AAN74817.2; -; Genomic_DNA.
DR EMBL; DS022242; EWG36205.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_018742396.1; XM_018886762.1.
DR AlphaFoldDB; Q8J2Q6; -.
DR SMR; Q8J2Q6; -.
DR STRING; 117187.FVEG_00325T0; -.
DR GeneID; 30058702; -.
DR KEGG; fvr:FVEG_00325; -.
DR eggNOG; KOG1178; Eukaryota.
DR OrthoDB; 1347336at2759; -.
DR Proteomes; UP000009096; Chromosome 1.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:1900541; P:fumonisin biosynthetic process; IDA:GO_Central.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF00550; PP-binding; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome.
FT CHAIN 1..548
FT /note="Nonribosomal peptide synthetase 8"
FT /id="PRO_0000441155"
FT DOMAIN 1..77
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 122..537
FT /note="Condensation"
FT MOD_RES 35
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 548 AA; 61622 MW; C94C0D781AFE9BE7 CRC64;
MNSLDQWRDT WAKVLSIQPS EIDDQDSFFD LGGDSVKAIQ LLSEAAQSAI NVDLQTFYDN
FWNIISPQLR GENRSGPIDR GGSIATGEAD DSIGLLKTDV NLEVVEKALS KVNIARESVC
RMAPISSIQE FFLYLGLNGH VGLINYVYQV EGRDLKQGLA RLVKHLEAKN PIFRTVMIED
DTGKFTQVQL SHSISTWTYP TDLQAYLDET MTGRQRLGAS PVRYSLVLKD ERHKGQNFFV
ISLDHTHCDA FSRYLIDKEI LQILKQPTEY ASLQNPERPW YGDFVKHNRA HILDEQLSRY
WASYMQGATL ANVHPLSEAV VGGELDGEMV EIVPIPVVSQ SRGTRGQTNP SHVILAAWAM
ALSKHSGLKD ITFGLARHGR SSDSFTDLRR VMGPLVTGTP FRVTLNDTQE RTEQLLNRVK
EEVLKTARWE QGMVPNIHPD AEGNPWVQSM VNLKSELYGF GNESWTGDEA EADITAIKMR
RDLQQYEFKS NWAILLSTLQ KQGQLRLRMY YQSQLLSHDK AQALFASFKS LIAELAAADG
SLVTGLLD
