ID   APF3_GIBF5              Reviewed;         295 AA.
AC   S0DLN5;
DT   07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT   18-SEP-2013, sequence version 1.
DT   03-AUG-2022, entry version 31.
DE   RecName: Full=Delta-1-pyrroline-5-carboxylate reductase apf3 {ECO:0000303|PubMed:25058475};
DE            EC=1.5.1.- {ECO:0000305|PubMed:25058475};
DE   AltName: Full=Apicidin F synthesis protein 3 {ECO:0000303|PubMed:25058475};
GN   Name=apf3 {ECO:0000303|PubMed:25058475}; ORFNames=FFUJ_00013;
OS   Gibberella fujikuroi (strain CBS 195.34 / IMI 58289 / NRRL A-6831) (Bakanae
OS   and foot rot disease fungus) (Fusarium fujikuroi).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium;
OC   Fusarium fujikuroi species complex.
OX   NCBI_TaxID=1279085;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=CBS 195.34 / IMI 58289 / NRRL A-6831;
RX   PubMed=23825955; DOI=10.1371/journal.ppat.1003475;
RA   Wiemann P., Sieber C.M.K., von Bargen K.W., Studt L., Niehaus E.-M.,
RA   Espino J.J., Huss K., Michielse C.B., Albermann S., Wagner D.,
RA   Bergner S.V., Connolly L.R., Fischer A., Reuter G., Kleigrewe K., Bald T.,
RA   Wingfield B.D., Ophir R., Freeman S., Hippler M., Smith K.M., Brown D.W.,
RA   Proctor R.H., Muensterkoetter M., Freitag M., Humpf H.-U., Gueldener U.,
RA   Tudzynski B.;
RT   "Deciphering the cryptic genome: genome-wide analyses of the rice pathogen
RT   Fusarium fujikuroi reveal complex regulation of secondary metabolism and
RT   novel metabolites.";
RL   PLoS Pathog. 9:E1003475-E1003475(2013).
RN   [2]
RP   FUNCTION, AND BIOTECHNOLOGY.
RX   PubMed=24195442; DOI=10.1021/np4006053;
RA   von Bargen K.W., Niehaus E.M., Bergander K., Brun R., Tudzynski B.,
RA   Humpf H.U.;
RT   "Structure elucidation and antimalarial activity of apicidin F: an
RT   apicidin-like compound produced by Fusarium fujikuroi.";
RL   J. Nat. Prod. 76:2136-2140(2013).
RN   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND INDUCTION.
RX   PubMed=25058475; DOI=10.1371/journal.pone.0103336;
RA   Niehaus E.M., Janevska S., von Bargen K.W., Sieber C.M., Harrer H.,
RA   Humpf H.U., Tudzynski B.;
RT   "Apicidin F: characterization and genetic manipulation of a new secondary
RT   metabolite gene cluster in the rice pathogen Fusarium fujikuroi.";
RL   PLoS ONE 9:E103336-E103336(2014).
CC   -!- FUNCTION: Delta-1-pyrroline-5-carboxylate reductase; part of the gene
CC       cluster that mediates the biosynthesis of the cyclic tetrapeptide
CC       apicidin F (APF) (PubMed:25058475). The non-ribosomal peptide
CC       synthetase apf1 incorporates four different amino acids to produce
CC       apicidin F: L-phenylalanine, D-pipecolic acid (D-pip), N-methoxy-L-
CC       tryptophan and L-2-aminooctanedioic acid (PubMed:25058475). L-
CC       Phenylalanine is the only proteinogenic amino acid directly used by
CC       apf1 (PubMed:24195442, PubMed:25058475). The 3 other apf1 substrates
CC       are non-proteinogenic and have to be modified by other enzymes of the
CC       cluster (PubMed:25058475). Lysine is converted to delta-1-pyrroline-5-
CC       carboxylate (P5C) which is reduced to L-pipecolic acid (L-pip) by apf3
CC       (PubMed:25058475). L-pip is epimerized to D-pip, probably by apf1
CC       activity, prior to incorporation (PubMed:25058475). L-Tryptophan is N-
CC       oxidyzed by one of the cytochrome P450 monooxygenases (apf7 or apf8),
CC       and further methylated at the hydroxy group by the O-methyltransferase
CC       apf6 to yield N-methoxy-L-tryptophan (PubMed:25058475). The synthesis
CC       of the fourth apf1 substrate is more complex (PubMed:25058475). The
CC       fatty acid synthase apf5 is involved in the synthesis of the octanoic
CC       acid backbone of L-2-aminooctanedioic acid by fixing one acetyl-CoA
CC       unit and three malonyl-CoA units (PubMed:25058475). Then one of the
CC       cytochrome P450 monooxygenases (apf7 or apf8) may oxidize this backbone
CC       to 2-oxooctanoic acid (PubMed:25058475). The aminotransferase apf4 is
CC       predicted to catalyze the exchange of the keto group with an amino
CC       group (PubMed:25058475). The next step would be the oxidation of 2-
CC       aminooctanoic acid by one of the cytochrome P450 monooxygenases (apf7
CC       or apf8). The last step is the oxidation of 2-amino-8-hydroxyoctanoic
CC       acid to 2-aminooctanedioic acid is catalyzed by the FAD-dependent
CC       monooxygenase apf9 (PubMed:25058475). {ECO:0000269|PubMed:24195442,
CC       ECO:0000269|PubMed:25058475}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:25058475}.
CC   -!- INDUCTION: Expression is positively regulated by the apicidin F
CC       cluster-specific transcription factor apf2 that binds to the eight-
CC       base-pair motif 5'-TGACGTGA-3' called the 'Api-box' that is found in
CC       all promoters of the apicidin F cluster except in the promoter region
CC       of apf2 itself (PubMed:25058475). {ECO:0000269|PubMed:25058475}.
CC   -!- DISRUPTION PHENOTYPE: Decreases 100-fold the apicidin F production.
CC       Leads to the incorporation of proline instead of D-pipecolic acid
CC       resulting in the production of apicidin J (PubMed:25058475).
CC       {ECO:0000269|PubMed:25058475}.
CC   -!- BIOTECHNOLOGY: Apicidin F, like the other known apicidins, is a cyclic
CC       tetrapeptides with anti-malarial properties via histone deacetylase
CC       inhibitory activity (PubMed:24195442). {ECO:0000269|PubMed:24195442}.
CC   -!- SIMILARITY: Belongs to the pyrroline-5-carboxylate reductase family.
CC       {ECO:0000305}.
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DR   EMBL; HF679023; CCT63351.1; -; Genomic_DNA.
DR   AlphaFoldDB; S0DLN5; -.
DR   SMR; S0DLN5; -.
DR   STRING; 1279085.S0DLN5; -.
DR   EnsemblFungi; CCT63351; CCT63351; FFUJ_00013.
DR   VEuPathDB; FungiDB:FFUJ_00013; -.
DR   HOGENOM; CLU_042344_0_1_1; -.
DR   BioCyc; MetaCyc:MON-19328; -.
DR   Proteomes; UP000016800; Chromosome 1.
DR   GO; GO:0004735; F:pyrroline-5-carboxylate reductase activity; IEA:InterPro.
DR   GO; GO:0006561; P:proline biosynthetic process; IEA:InterPro.
DR   HAMAP; MF_01925; P5C_reductase; 1.
DR   InterPro; IPR008927; 6-PGluconate_DH-like_C_sf.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR029036; P5CR_dimer.
DR   InterPro; IPR000304; Pyrroline-COOH_reductase.
DR   PANTHER; PTHR11645; PTHR11645; 1.
DR   Pfam; PF14748; P5CR_dimer; 1.
DR   PIRSF; PIRSF000193; Pyrrol-5-carb_rd; 1.
DR   SUPFAM; SSF48179; SSF48179; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   1: Evidence at protein level;
KW   Oxidoreductase; Reference proteome.
FT   CHAIN           1..295
FT                   /note="Delta-1-pyrroline-5-carboxylate reductase apf3"
FT                   /id="PRO_0000437158"
SQ   SEQUENCE   295 AA;  31217 MW;  B022F32F9843B851 CRC64;
     MPSSTSEDIT ACTFIGGGVM ARCMIDGLLD TYNNSVEIRV TARRSAHVGE LATRYPTLVV
     SQGNISPILW DEPWHKLGKT PAAHVVLICT QPWATSDVCQ DIRYVYSNYG FDPEPTFVTM
     CPGITTAQLE GWLPKGASVV RTMPNTPVAV RQGATALFAN KVVTAQQASA VADIFRAVSP
     QISFIKQEDG IDIAASISGS SPAYVFKLLA ILVEAGVSHG LAPDVAGALV KQSCLGAAMQ
     ALQDKRSLQS LIADVCVPGG STEKAMQRLD EGEFSAVVAA AVEKSLDANR AMGKE