Disease relevance of Chlorobiocin

• In the present study, the prenyltransferase involved in the biosynthesis of this moiety was identified from the clorobiocin producer (Streptomyces roseochromogenes), overexpressed, and purified [1].
• Clorobiocin was the most active compound both against E. coli DNA gyrase in vitro and against bacterial growth [2].
• Twenty-eight novel clorobiocin derivatives obtained from mutasynthesis experiments were investigated for their inhibitory activity towards Escherichia coli DNA gyrase and for their antibacterial activities towards clinically relevant gram-positive and gram-negative bacteria in comparison to novobiocin and clorobiocin [2].
• Antibacterial activity tests against Bacillus subtilis showed that novclobiocin 109 and novclobiocin 110 have antibacterial activities about eight times less than that of clorobiocin, whereas novclobiocin 104 showed no activity under the test conditions [3].

High impact information on Chlorobiocin

• CloQ from the clorobiocin biosynthetic gene cluster in Streptomyces roseochromogenes DS 12976 has recently been identified as a 4-hydroxyphenylpyruvate-3-dimethylallyltransferase [4].
• Their chemical structures contain amide bonds, formed between an aminocoumarin ring and an aromatic acyl component, which is 3-dimethylallyl-4-hydroxybenzoate in the case of novobiocin and clorobiocin [5].
• By gene inactivation, clo-hal was identified as the gene of the halogenase responsible for the introduction of the chlorine atom of clorobiocin [6].
• Novobiocin and clorobiocin are gyrase inhibitors produced by Streptomyces strains [7].
• When the 5-methylpyrrolyl-2-carboxyl-thioester of CouN1 is the cosubstrate, the in vitro product differs from clorobiocin only in a CH3 for Cl group change on the coumarin ring [8].

Chemical compound and disease context of Chlorobiocin

• Novobiocin, coumermycin A1, and clorobiocin, structurally related compounds that antagonize the B subunit of the essential bacterial enzyme DNA gyrase, were compared with 18 of their analogs for the inhibition of Escherichia coli DNA gyrase supertwisting activity in vitro and of bacterial multiplication [9].
• Three new antibiotics, vanillobiocin, isovanillobiocin and declovanillobiocin, were isolated from the culture broth of a cloQ-defective mutant of the clorobiocin producer Streptomyces roseochromogenes, which is blocked in the biosynthesis of the prenylated 4-hydroxybenzoic acid moiety of clorobiocin [10].
• Metabolic engineering of the heterologous production of clorobiocin derivatives and elloramycin in Streptomyces coelicolor M512 [11].

Biological context of Chlorobiocin

• To understand the difference in affinity, in order that this information might be exploited in rational drug design, the crystal structure of the 24-kDa GyrB fragment in complex with clorobiocin was determined to high resolution [12].
• Although a derivative of ColE1-pBR322 was effectively cured by clorobiocin, the ColE1 plasmid was resistant to its effect [13].
• In this study, the genes cloN1 and cloN7 were deleted separately from a cosmid containing the complete clorobiocin cluster [14].
• CloN6, a novel methyltransferase catalysing the methylation of the pyrrole-2-carboxyl moiety of clorobiocin [3].
• Correlation of hydrophobicity with protein binding for clorobiocin analogs [15].

Associations of Chlorobiocin with other chemical compounds

• Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters [16].
• The biosynthetic gene clusters of the gyrase inhibitors coumermycin A(1) and clorobiocin contain two different resistance genes (gyrB(R) and parY(R)) [17].
• In contrast to the results obtained with clorobiocin, inhibition of cell division by the beta-lactam antibiotic cefuroxime did not cause any detectable disturbance in the rate of synthesis of either inner or outer membrane protein [18].

Gene context of Chlorobiocin

• However, unlike other inhibitors of deoxyribonucleic acid synthesis, clorobiocin failed to induce the synthesis of protein X, the recA gene product [19].
• Clorobiocin, an inhibitor of the gyrB subunit of DNA gyrase, was used for the curing of some Escherichia coli plasmids [13].
• Antimicrobial and DNA gyrase-inhibitory activities of novel clorobiocin derivatives produced by mutasynthesis [2].
• In this work, we obtained the crystal costructures of the natural coumarin clorobiocin and a synthetic analogue with the 24 kDa gyrase fragment [20].
• Metabolic engineering of aminocoumarins: inactivation of the methyltransferase gene cloP and generation of new clorobiocin derivatives in a heterologous host [21].

Analytical, diagnostic and therapeutic context of Chlorobiocin

• Moreover, to understand the differences in energetics of binding of clorobiocin and novobiocin to the protein, the results from isothermal titration calorimetry are also presented [12].
• However, sequence analysis of the clorobiocin biosynthetic gene cluster did not reveal a gene with sequence similarity to the SAM-dependent methyltransferases that could be assigned to this reaction [3].
• Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics [22].
• Crystallization and preliminary X-ray analysis of the aromatic prenyltransferase CloQ from the clorobiocin biosynthetic cluster of Streptomyces roseochromogenes [23].

References