Hybrid antibiotics

The yields of DNA intake by the cells are, however, very low. The few bacteria containing the hybrid plasmid need to be sorted out. One technique applies a plasmid which encodes for antibiotic-degrading enzymes, e.g for penicillinase and tetracyclinase, and thus... 

Coeffet-Le Gal, M.F., Thurston, L., Rich, P. et al. (2006) Complementation of daptomycin dpt A and dptD deletion mutations in trans and production of hybrid lipopeptide antibiotics. Microbiology (Reading, England), 152,2993. 

Miao, V., Coeffet-Le Gal, M.-F., Nguyen, K. et al. (2006) Genetic engineering in Streptomyces roseosporus to produce hybrid lipopeptide antibiotics. Chemistry Biology, 13, 269. 

The intersubunit rotation is required for translocation as ribosomes trapped in the nonrotated state by an engineered intersubunit disulfide bridge fail in tRNA-mRNA movement. Real-time observation of intersubunit movement by fluorescence resonance energy transfer (FRET) showed that intersubunit movement occurs concomitantly with hybrid state formation, and that the rotated state can be trapped by the antibiotic viomycin. Similarly to the fluctuation of tRNAs between classical and hybrid states, single-molecule studies have detected spontaneous intersubunit movement where the 3 OS subunit fluctuates between a rotated... 

Robertson GT, Bonventre El, Doyle TB, Du Q, Duncan L, Morris TW, Roche ED, Yan D, Lynch AS. (2008) In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic Studies of the mode of action in Staphylococcus aureus. Antimicrob Agents Chemother 52 2313-2323. 

Of those small molecules best able to bind DNA-RNA hybrids, very few have been found. At last count, the number was less than ten. For comparison, the nnmber of molecules known to target duplex DNA is perhaps in the thousands. Few reported attempts have been made to target the unique structure of the DNA-RNA hybrids, and consequently only a handful of molecules have been identified. " " A few years ago, we identified aminoglycosides as the antibiotics most likely to stimnlate groove-based recognition of A-form nucleic acid... 

The process design principles of SLM, non-dispersive extraction, and hybrid hquid membrane systems need to be understood through bench scale experiments using feed solution of practical relevance. While the economic analysis of an ELM process can be performed from small scale experiments, such an analysis is difficult for other LM systems. In particular, availability and cost of hollow fiber membranes for commercial application are not known apriori. A simple rule of thumb for cost scale-up may not be apphcable in the case of an HE membrane. Yet we feel that the pilot plant tests would be adequate to make realistic cost benefit analysis of a liquid membrane process, since the volume of production in )8-lactam antibiotic industries is usually low. 

The reported strategies utilized in DNA sensing include (1) sequence-specific hybridization processes based on the oxidation signal of most electroactive DNA bases, guanine and adenine [13,24] or (2) quasi-specific detection of small molecules capable of binding by intercalation or complexation with DNA, such as metal coordination complexes, antibiotics, pesticides, pollutants, etc. [17,18] or in the presence of some metal tags such as gold, silver nanoparticles, etc. [23,50,51]. 

Solenberg PJ, Matsushima P, Stack DR et al (1997) Production of hybrid glycopeptide antibiotics in vitro and in Streptomyces toyocaensis. Chem Biol 4 195-202... 

Homeologous recombination (recombination between partially homologous sequences) has been successfully used to produce novel antibiotics and functional hybrid proteins in Streptomyces [64-66], If partially homologous sequences are placed in tandem and in the same orientation [67,68], general recombination leads to excision of the duplicated genes as well as of the sequences lying between... 

Presence (+) or absence (—) of acyltransferase activity for 16-membered macrolide antibiotics. b Presence (+) or absence (—) of hybridizing band(s) in Southern blot analysis using acyA or acyBl as a probe. " Weakly hybridizing bands were detected. 

JK Epp, MLB Huber, JR Turner, T Goodson, and BE Schoner. Production of a hybrid macrolide antibiotic in Streptomyces ambofaciens and Streptomyces lividans by introduction of a cloned carbomycin biosynthetic gene from Streptomyces ther-motolerans. Gene 85 293-301, 1989. 

A Arisawa, N Kawamura, K Takeda, H Tsunekawa, K Okamura, R Okamoto. Cloning of the macrolide antibiotic biosynthesis gene acyA, which encodes 3-0-acyltransferase, from Streptomyces thermotolerans and its use for direct fermentative production of a hybrid macrolide antibiotic. Appl Environ Microbiol 60 2657-2660, 1994. 

Figure 23 Altering chain extension by DEBS. A hybrid PKS was constructed by introducing malonate-specific ATs in place of the methylmalonate-specific AT, of DEBS. The resultant erythromycin analog lacked both the C-12 methyl and C-12 hydroxyl groups of the parent antibiotic.

L Katz, S Donadio. Polyketide synthesis prospects for hybrid antibiotics. Annu Rev Microbiol 875-912, 1993. 

Another example of ozonolysis being used in the production of penem-type antibiotics, which are regarded as a hybrid between penicillins and cephalosporins, has been demonstrated by Osborne and colleagues82 who describe the convenient and chiral synthesis of the triazolymethylene penem 85, from 6-aminopenicillanic acid (6-APA) (86), an inexpensive and readily available chiral synthon. The multi-step synthesis incorporates a key synthetic step involving the ozonolytic cleavage of a double bond in 87 to produce an amide 88 (Scheme 11.23). 

Strassert CA et al (2009) Photoactive hybrid nanomaterial for targeting, labeling, and killing antibiotic-resistant bacteria. Angew Chem Int Ed 48 7928-7931... 

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