Aklanonic acid methyl ester cyclase AcmA

Details

Name
Aklanonic acid methyl ester cyclase AcmA
Kind
protein
Synonyms
  • 5.5.1.23
  • AAME cyclase
  • aknH
  • Methyl aklanonate cyclase
Gene Name
acma
UniProtKB Entry
O52646Swiss-Prot
Organism
Streptomyces galilaeus
NCBI Taxonomy ID
33899
Amino acid sequence
>lcl|BSEQ0022075|Aklanonic acid methyl ester cyclase AcmA
MSEQIAAVRRMVEAYNTGKTDDVADYIHPEYMNPGTLEFTSLRGPELFAINVAWVKKTFS
EEARLEEVGIEERADWVRARLVLYGRHVGEMVGMAPTGRLFSGEQIHLLHFVDGKIHHHR
DWPDYQGTYRQLGEPWPETEHRRP
Number of residues
144
Molecular Weight
16730.765
Theoretical pI
6.08
GO Classification
Functions
intramolecular lyase activity
Processes
antibiotic biosynthetic process / daunorubicin biosynthetic process / doxorubicin metabolic process
General Function
Involved in the biosynthesis of aklavinone which is an important precursor common to the formation of the clinically significant anthracyclines such as carminomycin, daunorubicin (daunomycin), rhodomycin, aclacinomycin T (aklavin) and aclacinomycin A (aclarubicin). These compounds are aromatic polyketide antibiotics that exhibit high cytotoxicity and are widely applied in the chemotherapy of a variety of cancers. Catalyzes the cyclization of aklanonic acid methyl ester to yield aklaviketone. It is also able to use nogalonic acid methyl ester as substrate, but produces exclusively auraviketone with C9-R stereochemistry.
Specific Function
intramolecular lyase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Not Available
Gene sequence
>lcl|BSEQ0006516|435 bp
GTGAGTGAGCAGATAGCGGCCGTTCGGCGCATGGTCGAGGCGTACAACACCGGAAAAACG
GATGATGTGGCCGACTACATCCATCCGGAATACATGAATCCGGGAACCCTGGAATTCACC
TCGCTGCGTGGCCCGGAACTCTTCGCGATCAATGTCGCGTGGGTCAAGAAGACGTTCTCC
GAGGAGGCGCGGCTGGAAGAGGTCGGCATCGAGGAGCGGGCCGACTGGGTGCGCGCCCGG
CTGGTGCTCTACGGCCGGCACGTCGGTGAGATGGTCGGCATGGCGCCGACCGGACGGCTG
TTCTCCGGCGAGCAGATCCATCTCCTGCACTTCGTCGACGGGAAGATCCACCACCACCGC
GACTGGCCCGACTACCAGGGCACCTACCGCCAGCTCGGCGAGCCGTGGCCGGAGACCGAG
CACCGCCGTCCCTGA
Chromosome Location
Not Available
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDO52646
UniProtKB Entry NameDNRD_STRGJ
GenBank Gene IDAF043550
PDB ID(s)2F98, 2F99
KEGG IDag:AAF70112
General References
  1. Kantola J, Kunnari T, Hautala A, Hakala J, Ylihonko K, Mantsala P: Elucidation of anthracyclinone biosynthesis by stepwise cloning of genes for anthracyclines from three different Streptomyces spp. Microbiology. 2000 Jan;146 ( Pt 1):155-63. [Article]
  2. Raty K, Kantola J, Hautala A, Hakala J, Ylihonko K, Mantsala P: Cloning and characterization of Streptomyces galilaeus aclacinomycins polyketide synthase (PKS) cluster. Gene. 2002 Jun 26;293(1-2):115-22. [Article]
  3. Chung JY, Fujii I, Harada S, Sankawa U, Ebizuka Y: Expression, purification, and characterization of AknX anthrone oxygenase, which is involved in aklavinone biosynthesis in Streptomyces galilaeus. J Bacteriol. 2002 Nov;184(22):6115-22. [Article]
  4. Kallio P, Sultana A, Niemi J, Mantsala P, Schneider G: Crystal structure of the polyketide cyclase AknH with bound substrate and product analogue: implications for catalytic mechanism and product stereoselectivity. J Mol Biol. 2006 Mar 17;357(1):210-20. Epub 2006 Jan 6. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
DERIVATIVE OF AKLANONIC ACID METHYL ESTER (AAME)experimentalunknowntargetDetails