Disease relevance of Aklavinone

• Aclacinomycin methylesterase (RdmC) is one of the tailoring enzymes that modify the aklavinone skeleton in the biosynthesis of anthracyclines in Streptomyces species [1].
• This result indicated that the aklavinone 11-hydroxylase gene was stably expressed in S. galilaeus ATCC 31133 and that it gave rise to a hybrid aclacinomycin A which showed highly specific in vitro cytotoxicity against leukemia and melanoma cell lines [2].

High impact information on Aklavinone

• Transformation of S. galilaeus ATCC 31133 with plasmid pMC213 containing the aklavinone 11-hydroxylase gene (dnrF) resulted in the production of many red pigments [2].
• The aklavinone 11-hydroxylase gene and two doxorubicin resistance genes cloned from Streptomyces peucetius subsp. caesius ATCC 27952 were introduced into doxorubicin-sensitive Streptomyces galilaeus ATCC 31133, an aclacinomycin producer [2].
• Extracts of Streptomyces lividans TK24 containing recombinant DauE catalyzed the NADPH-specific conversion of aklaviketone, maggiemycin, and 7-oxodaunomycinone to aklavinone, epsilon-rhodomycinone, and daunomycinone, respectively [3].
• A 3.4-kb BamHI fragment that is assumed to be a part of the aklavinone biosynthetic gene cluster of Streptomyces galilaeus 3AR-33 and contains the genes required for the early stage of polyketide biosynthesis was sequenced [4].
• Cloning and sequence analysis of the aknA region of the 2-hydroxyaklavinone-producing strain S. galilaeus ANR-58 identified an alteration in the gene, confirming that the aknA gene is essential for aklavinone biosynthesis [4].

Chemical compound and disease context of Aklavinone

• Heterologous expression of dnrF in Streptomyces lividans TK23 and in Escherichia coli demonstrated that the gene encodes a NADPH-dependent hydroxylase catalysing the hydroxylation of aklavinone to yield epsilon-rhodomycinone [5].
• The dnrF gene, responsible for conversion of aklavinone to epsilon-rhodomycinone via C-11 hydroxylation, was mapped in the daunorubicin (Dnr) gene cluster of Streptomyces peucetius ATCC 29050, close to drrAB, one of the anthracycline-resistance genes [5].
• The rdm genes B, C and E from Streptomyces purpurascens encode enzymes that tailor aklavinone and aclacinomycins [6].
• New anthracycline metabolites from mutant strains of Streptomyces galilaeus MA144-M1. II. Structure of 2-hydroxyaklavinone and new aklavinone glycosides [7].
• Microbial conversion of beta-rhodomycinone and aklavinone using an aclarubicin-negative Streptomyces galilaeus mutant afforded new anthracycline antibiotics CG21-C and CG1-C which had a rednosyl-2-deoxyfucosyl-rhodosaminyl trisaccharide residue at C-7 of each added aglycone [8].

Biological context of Aklavinone

• The phenotype of a dnrF mutant generated by gene disruption supports the idea that the dnrF gene encodes aklavinone 11-hydroxylase [9].
• Strain H039 accumulated aklavinone and H026, H035, H038 and H054 had mutations that changed glycosylation of aklavinone [10].
• Respective products deduced from ORF1, ORF2, ORF3, and ORF5 were similar to the penicillin-binding protein 4 of Streptomyces lactamduras, the repressor protein AcrR of the acrAB operon, the enzyme RdmC involved in the biosynthesis of the antibiotic aklavinone, and IS801 transposase-like protein from Pseudomonas pseudoalcakigenes, respectively [11].

Associations of Aklavinone with other chemical compounds

• Accordingly, when aclacinomycins minimal PKS genes were substituted for those of nogalamycin in the plasmid carrying genes for auramycinone biosynthesis, aklavinone was produced in the heterologous hosts [12].

Gene context of Aklavinone

• When S. galilaeus ATCC 31671 was transformed with a plasmid carrying only the intact actIII gene (pANT45), aklavinone was formed exclusively [13].

Analytical, diagnostic and therapeutic context of Aklavinone

• Molecular cloning and characterization of the aklavinone 11-hydroxylase gene of Streptomyces peucetius subsp. caesius ATCC 27952 [9].
• The transformant produced aklavinone according to TLC and HPLC analyses [14].

References