ID   DNRD_STRPE              Reviewed;         145 AA.
AC   Q54808;
DT   19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   03-AUG-2022, entry version 47.
DE   RecName: Full=Aklanonic acid methyl ester cyclase DnrD;
DE            Short=AAME cyclase;
DE            EC=5.5.1.23;
DE   AltName: Full=Methyl aklanonate cyclase;
GN   Name=dnrD;
OS   Streptomyces peucetius.
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=1950;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC   STRAIN=ATCC 29050 / DSM 40754 / JCM 9920 / NBRC 100596 / NCIMB 10972;
RX   PubMed=7601857; DOI=10.1128/jb.177.13.3879-3884.1995;
RA   Madduri K., Hutchinson C.R.;
RT   "Functional characterization and transcriptional analysis of a gene cluster
RT   governing early and late steps in daunorubicin biosynthesis in Streptomyces
RT   peucetius.";
RL   J. Bacteriol. 177:3879-3884(1995).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MASS
RP   SPECTROMETRY, AND REACTION MECHANISM.
RC   STRAIN=ATCC 29050 / DSM 40754 / JCM 9920 / NBRC 100596 / NCIMB 10972;
RX   PubMed=10200167; DOI=10.1021/bi9827924;
RA   Kendrew S.G., Katayama K., Deutsch E., Madduri K., Hutchinson C.R.;
RT   "DnrD cyclase involved in the biosynthesis of doxorubicin: purification and
RT   characterization of the recombinant enzyme.";
RL   Biochemistry 38:4794-4799(1999).
CC   -!- FUNCTION: Involved in the biosynthesis of aklavinone which is an
CC       important precursor common to the formation of the clinically
CC       significant anthracyclines such as carminomycin, daunorubicin
CC       (daunomycin), rhodomycin, aclacinomycin T (aklavin) and aclacinomycin A
CC       (aclarubicin). These compounds are aromatic polyketide antibiotics that
CC       exhibit high cytotoxicity and are widely applied in the chemotherapy of
CC       a variety of cancers. Catalyzes the cyclization of aklanonic acid
CC       methyl ester to yield aklaviketone presumably via an intramolecular
CC       aldol condensation mechanism, although water is not eliminated.
CC       {ECO:0000269|PubMed:10200167, ECO:0000269|PubMed:7601857}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=methyl aklanonate = aklaviketone; Xref=Rhea:RHEA:37879,
CC         ChEBI:CHEBI:77988, ChEBI:CHEBI:77994; EC=5.5.1.23;
CC         Evidence={ECO:0000269|PubMed:10200167, ECO:0000269|PubMed:7601857};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=52.1 uM for aklanonic acid methyl ester (at pH 7 and at 30 degrees
CC         Celsius) {ECO:0000269|PubMed:10200167};
CC         Vmax=14.3 umol/min/mg enzyme (at pH 7 and at 30 degrees Celsius)
CC         {ECO:0000269|PubMed:10200167};
CC       pH dependence:
CC         Optimum pH is 7. The enzyme is active between pH 5.0 and 9.0.
CC         {ECO:0000269|PubMed:10200167};
CC   -!- PATHWAY: Antibiotic biosynthesis; daunorubicin biosynthesis.
CC   -!- PATHWAY: Antibiotic biosynthesis; carminomycin biosynthesis.
CC   -!- PATHWAY: Antibiotic biosynthesis; rhodomycin biosynthesis.
CC   -!- PATHWAY: Antibiotic biosynthesis; aclacinomycin biosynthesis.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC   -!- MASS SPECTROMETRY: Mass=16572; Method=Electrospray;
CC       Evidence={ECO:0000269|PubMed:10200167};
CC   -!- MISCELLANEOUS: In contrast to the analogous intramolecular aldol
CC       cyclization catalyzed by TcmI, the conversion catalyzed by DnrD occurs
CC       after anthraquinone formation and requires activation of a carboxylic
CC       acid group by esterification of aklanonic acid, the aklanonic acid
CC       methyl ester precursor. {ECO:0000305|PubMed:10200167}.
CC   -!- SIMILARITY: Belongs to the polyketide cyclase DnrD family.
CC       {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; L40425; AAA99000.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q54808; -.
DR   SMR; Q54808; -.
DR   KEGG; ag:AAA99000; -.
DR   UniPathway; UPA00054; -.
DR   UniPathway; UPA01040; -.
DR   UniPathway; UPA01042; -.
DR   UniPathway; UPA01043; -.
DR   GO; GO:0016872; F:intramolecular lyase activity; IDA:UniProtKB.
DR   GO; GO:0017000; P:antibiotic biosynthetic process; IDA:UniProtKB.
DR   GO; GO:1901771; P:daunorubicin biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0044598; P:doxorubicin metabolic process; IDA:UniProtKB.
DR   InterPro; IPR009959; Cyclase_SnoaL-like.
DR   InterPro; IPR032710; NTF2-like_dom_sf.
DR   PANTHER; PTHR38436; PTHR38436; 1.
DR   Pfam; PF07366; SnoaL; 1.
DR   SUPFAM; SSF54427; SSF54427; 1.
PE   1: Evidence at protein level;
KW   Antibiotic biosynthesis; Isomerase.
FT   INIT_MET        1
FT                   /note="Removed"
FT   CHAIN           2..145
FT                   /note="Aklanonic acid methyl ester cyclase DnrD"
FT                   /id="PRO_0000425672"
FT   BINDING         106
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   145 AA;  16701 MW;  4FDA0DB5C4972EDD CRC64;
     MSTQIDLVRR MVEAYNTGKT DDVAEFIHLE YLNPGALEHN PELRGPEAFA AAVTWLKYAF
     SEEAHLEEIE YEENGPWVRA KLALYGRHVG NLVGMPATGR RFSGEQIHLI RIVDGKIRDH
     RDWPDYLGTY RQLGEPWPTP EGWRP