DNRD_STRGJ
ID DNRD_STRGJ Reviewed; 144 AA.
AC O52646;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Aklanonic acid methyl ester cyclase AcmA;
DE Short=AAME cyclase;
DE EC=5.5.1.23;
DE AltName: Full=Methyl aklanonate cyclase;
GN Name=acma; Synonyms=aknH;
OS Streptomyces galilaeus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=33899;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND SUBSTRATE SPECIFICITY.
RC STRAIN=ATCC 31615;
RX PubMed=10658662; DOI=10.1099/00221287-146-1-155;
RA Kantola J., Kunnari T., Hautala A., Hakala J., Ylihonko K., Mantsala P.;
RT "Elucidation of anthracyclinone biosynthesis by stepwise cloning of genes
RT for anthracyclines from three different Streptomyces spp.";
RL Microbiology 146:155-163(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC31615;
RX PubMed=12137949; DOI=10.1016/s0378-1119(02)00699-6;
RA Raty K., Kantola J., Hautala A., Hakala J., Ylihonko K., Mantsala P.;
RT "Cloning and characterization of Streptomyces galilaeus aclacinomycins
RT polyketide synthase (PKS) cluster.";
RL Gene 293:115-122(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=3AR-33;
RX PubMed=12399480; DOI=10.1128/jb.184.22.6115-6122.2002;
RA Chung J., Fujii I., Tsukamoto N., Sankawa U., Ebizuka Y.;
RT "Expression, purification, and characterization of AknX anthrone oxygenase,
RT which is involved in aklavinone biosynthesis in Streptomyces galilaeus.";
RL J. Bacteriol. 184:6115-6122(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC31615;
RA Niemi J.;
RL Submitted (AUG-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 2-144 IN COMPLEX WITH SUBSTRATE
RP ANALOGS, FUNCTION, MUTAGENESIS OF TYR-15; ASN-51; GLN-105; HIS-107 AND
RP ASP-121, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, REACTION
RP MECHANISM, AND SUBUNIT.
RX PubMed=16414075; DOI=10.1016/j.jmb.2005.12.064;
RA Kallio P., Sultana A., Niemi J., Mantsala P., Schneider G.;
RT "Crystal structure of the polyketide cyclase AknH with bound substrate and
RT product analogue: implications for catalytic mechanism and product
RT stereoselectivity.";
RL J. Mol. Biol. 357:210-220(2006).
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. It is also able to use nogalonic
CC acid methyl ester as substrate, but produces exclusively auraviketone
CC with C9-R stereochemistry. {ECO:0000269|PubMed:10658662,
CC ECO:0000269|PubMed:16414075}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2 uM for nogalonic acid methyl ester
CC {ECO:0000269|PubMed:16414075};
CC Note=kcat is 1 sec(-1) for cyclization with nogalonic acid methyl
CC ester.;
CC pH dependence:
CC Optimum pH is 7.2. {ECO:0000269|PubMed:16414075};
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:0000269|PubMed:16414075}.
CC -!- SIMILARITY: Belongs to the polyketide cyclase DnrD family.
CC {ECO:0000305}.
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DR EMBL; AF043550; AAB99853.1; -; Genomic_DNA.
DR EMBL; AF257324; AAF70112.1; -; Genomic_DNA.
DR EMBL; AB008466; BAB72051.1; -; Genomic_DNA.
DR PDB; 2F98; X-ray; 2.10 A; A/B/C/D=2-144.
DR PDB; 2F99; X-ray; 1.90 A; A/B/C/D=2-144.
DR PDBsum; 2F98; -.
DR PDBsum; 2F99; -.
DR AlphaFoldDB; O52646; -.
DR SMR; O52646; -.
DR DrugBank; DB04624; DERIVATIVE OF AKLANONIC ACID METHYL ESTER (AAME).
DR KEGG; ag:AAF70112; -.
DR BioCyc; MetaCyc:MON-18179; -.
DR BRENDA; 5.5.1.23; 13206.
DR BRENDA; 5.5.1.B6; 13206.
DR UniPathway; UPA00054; -.
DR UniPathway; UPA01040; -.
DR UniPathway; UPA01042; -.
DR UniPathway; UPA01043; -.
DR EvolutionaryTrace; O52646; -.
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 3D-structure; Antibiotic biosynthesis; Isomerase.
FT CHAIN 1..144
FT /note="Aklanonic acid methyl ester cyclase AcmA"
FT /id="PRO_0000425673"
FT BINDING 51
FT /ligand="substrate"
FT BINDING 105
FT /ligand="substrate"
FT MUTAGEN 15
FT /note="Y->F: Retains 45% of cyclase activity with a partial
FT loss in stereoselectivity of the final product (20% of C9-S
FT and 80% of C9-R isomers). Retains 20% of cyclase activity
FT with a total loss in stereoselectivity of the final product
FT (racemic mixture of both stereoisomers); when associated
FT with L-51."
FT /evidence="ECO:0000269|PubMed:16414075"
FT MUTAGEN 51
FT /note="N->L: Retains 20% of cyclase activity with a total
FT loss in stereoselectivity of the final product (racemic
FT mixture of both stereoisomers); when associated with F-15."
FT /evidence="ECO:0000269|PubMed:16414075"
FT MUTAGEN 105
FT /note="Q->A: Retains significant cyclase activity (100% of
FT C9-R isomer)."
FT /evidence="ECO:0000269|PubMed:16414075"
FT MUTAGEN 107
FT /note="H->A: Retains significant cyclase activity (100% of
FT C9-R isomer)."
FT /evidence="ECO:0000269|PubMed:16414075"
FT MUTAGEN 121
FT /note="D->A: Loss of cyclase activity."
FT /evidence="ECO:0000269|PubMed:16414075"
FT HELIX 3..17
FT /evidence="ECO:0007829|PDB:2F99"
FT HELIX 23..25
FT /evidence="ECO:0007829|PDB:2F99"
FT STRAND 27..32
FT /evidence="ECO:0007829|PDB:2F99"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:2F99"
FT TURN 37..39
FT /evidence="ECO:0007829|PDB:2F99"
FT HELIX 44..59
FT /evidence="ECO:0007829|PDB:2F99"
FT STRAND 64..73
FT /evidence="ECO:0007829|PDB:2F99"
FT STRAND 76..86
FT /evidence="ECO:0007829|PDB:2F99"
FT STRAND 100..112
FT /evidence="ECO:0007829|PDB:2F99"
FT STRAND 115..123
FT /evidence="ECO:0007829|PDB:2F99"
FT HELIX 125..131
FT /evidence="ECO:0007829|PDB:2F99"
SQ SEQUENCE 144 AA; 16731 MW; 30083BDD35E808C0 CRC64;
MSEQIAAVRR MVEAYNTGKT DDVADYIHPE YMNPGTLEFT SLRGPELFAI NVAWVKKTFS
EEARLEEVGI EERADWVRAR LVLYGRHVGE MVGMAPTGRL FSGEQIHLLH FVDGKIHHHR
DWPDYQGTYR QLGEPWPETE HRRP
