ID   RAPL_STRRN              Reviewed;         343 AA.
AC   Q54304; A0A0A0NQJ4;
DT   16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT   23-MAY-2018, sequence version 2.
DT   03-AUG-2022, entry version 82.
DE   RecName: Full=L-lysine cyclodeaminase;
DE            EC=4.3.1.28;
DE   AltName: Full=Rapamycin biosynthesis protein L;
GN   Name=rapL; ORFNames=M271_40660 {ECO:0000312|EMBL:AGP59511.1};
OS   Streptomyces rapamycinicus (strain ATCC 29253 / DSM 41530 / NRRL 5491 /
OS   AYB-994) (Streptomyces hygroscopicus (strain ATCC 29253)).
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces; Streptomyces violaceusniger group.
OX   NCBI_TaxID=1343740;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 29253 / DSM 41530 / NRRL 5491 / AYB-994;
RX   PubMed=8635756; DOI=10.1016/0378-1119(95)00800-4;
RA   Aparicio J.F., Molnar I., Schwecke T., Koenig A., Haydock S.F., Khaw L.E.,
RA   Staunton J., Leadlay P.F., Staunton J., Leadlay P.F.;
RT   "Organization of the biosynthetic gene cluster for rapamycin in
RT   Streptomyces hygroscopicus: analysis of the enzymatic domains in the
RT   modular polyketide synthase.";
RL   Gene 169:9-16(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29253 / DSM 41530 / NRRL 5491 / AYB-994;
RX   PubMed=23929477; DOI=10.1128/genomea.00581-13;
RA   Baranasic D., Gacesa R., Starcevic A., Zucko J., Blazic M., Horvat M.,
RA   Gjuracic K., Fujs S., Hranueli D., Kosec G., Cullum J., Petkovic H.;
RT   "Draft genome sequence of Streptomyces rapamycinicus strain NRRL 5491, the
RT   producer of the immunosuppressant rapamycin.";
RL   Genome Announc. 1:E00581-E00581(2013).
RN   [3]
RP   DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 29253 / DSM 41530 / NRRL 5491 / AYB-994;
RX   PubMed=9473033; DOI=10.1128/jb.180.4.809-814.1998;
RA   Khaw L.E., Bohm G.A., Metcalfe S., Staunton J., Leadlay P.F.;
RT   "Mutational biosynthesis of novel rapamycins by a strain of Streptomyces
RT   hygroscopicus NRRL 5491 disrupted in rapL, encoding a putative lysine
RT   cyclodeaminase.";
RL   J. Bacteriol. 180:809-814(1998).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR,
RP   ACTIVITY REGULATION, AND PATHWAY.
RC   STRAIN=ATCC 29253 / DSM 41530 / NRRL 5491 / AYB-994;
RX   PubMed=16536560; DOI=10.1021/ja0587603;
RA   Gatto G.J. Jr., Boyne M.T. II, Kelleher N.L., Walsh C.T.;
RT   "Biosynthesis of pipecolic acid by RapL, a lysine cyclodeaminase encoded in
RT   the rapamycin gene cluster.";
RL   J. Am. Chem. Soc. 128:3838-3847(2006).
CC   -!- FUNCTION: Converts L-lysine to L-pipecolate, which is incorporated into
CC       multiple secondary metabolite products, including rapamycin, tobulysin,
CC       virginiamycin and pristinamycin. {ECO:0000269|PubMed:16536560}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysine = L-pipecolate + NH4(+); Xref=Rhea:RHEA:34303,
CC         ChEBI:CHEBI:28938, ChEBI:CHEBI:32551, ChEBI:CHEBI:61185; EC=4.3.1.28;
CC         Evidence={ECO:0000269|PubMed:16536560};
CC   -!- COFACTOR:
CC       Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC         Evidence={ECO:0000269|PubMed:16536560};
CC   -!- ACTIVITY REGULATION: Inhibited by nipecotic acid and thiazolidine-2-
CC       carboxylic acid. {ECO:0000269|PubMed:16536560}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=46 uM for L-lysine {ECO:0000269|PubMed:16536560};
CC         Note=kcat is 0.61 min(-1) with L-lysine as substrate.;
CC   -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:16536560}.
CC   -!- DISRUPTION PHENOTYPE: Cells do not produce significant amounts of
CC       rapamycin. Cells supplemented by L-pipecolate restore levels of
CC       rapamycin. {ECO:0000269|PubMed:9473033}.
CC   -!- SIMILARITY: Belongs to the ornithine cyclodeaminase/mu-crystallin
CC       family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X86780; CAA60467.1; -; Genomic_DNA.
DR   EMBL; CP006567; AGP59511.1; -; Genomic_DNA.
DR   PIR; T30233; T30233.
DR   AlphaFoldDB; Q54304; -.
DR   SMR; Q54304; -.
DR   STRING; 1343740.M271_40660; -.
DR   KEGG; ag:CAA60467; -.
DR   KEGG; src:M271_40660; -.
DR   PATRIC; fig|1343740.8.peg.6275; -.
DR   eggNOG; COG2423; Bacteria.
DR   HOGENOM; CLU_042088_3_2_11; -.
DR   BioCyc; MetaCyc:MON-17627; -.
DR   GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.1780.10; -; 1.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR003462; ODC_Mu_crystall.
DR   InterPro; IPR023401; ODC_N.
DR   PANTHER; PTHR13812; PTHR13812; 1.
DR   Pfam; PF02423; OCD_Mu_crystall; 1.
DR   PIRSF; PIRSF001439; CryM; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; Lyase; NAD.
FT   CHAIN           1..343
FT                   /note="L-lysine cyclodeaminase"
FT                   /id="PRO_0000423987"
FT   CONFLICT        50
FT                   /note="T -> P (in Ref. 1; CAA60467)"
FT   CONFLICT        84
FT                   /note="Q -> E (in Ref. 1; CAA60467)"
FT   CONFLICT        102
FT                   /note="D -> G (in Ref. 1; CAA60467)"
FT   CONFLICT        127..129
FT                   /note="AVA -> SVT (in Ref. 1; CAA60467)"
SQ   SEQUENCE   343 AA;  36091 MW;  84617294E585BB51 CRC64;
     MQTKVLCQRD IKRILSVVGR DVMMDRLISE VHAGFARLGR GETDEPPPRT GFARGGDVPG
     VIEFMPHRAS GIGVTMKTVS YSPQNFERFN LPTIVGTVSR LDDDSGSMVA LADAATITAM
     RTGAVAAVAT RLLARPGSTT LALIGAGAQA VTQAHALSRV LPLERILISD IKAEHAESFA
     GRVAFLELPV EVTDAATAMA TADVLCTVTS VPVGGGPVVP AEPRQAHLHV NGIGADEQGK
     TELPKALLDD AFICVDHPGQ ARAEGEFQQL PDRELGPSLA DLCAAPEIAA PHPERLSVFD
     STGSAFADHI ALDVLLGFAD ELGLGHKMSI ESTPEDVLDP YSL