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1

From DNA sequence to antibiotic

100%

Pawlik K., Kotowska M.

Biotechnologia

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2005

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issue 3

57-74

EN

Progress in molecular biology, large number of known bacterial sequences and a number of microbiological genome sequencing projects finished or running allow to think about creating in vitro the DNA code in order to obtain new metabolites. Here, we describe the attempts of biosynthesis of new polyketides by designing new genes coding polyketide synthases. In assembling new polyketide synthases, the fragments of known genes are widely used. High homology of the polyketide synthase genes and a number of known produced polyketides give a possibility to describe a polyketide synthase on a DNA sequence level. Basing on known amino acid motifs, it is possible to determine enzymatic activities acting in the process of polyketide synthesis, and so to predict putative structure of the final metabolite. Successful artificial synthesis of 6-deoxyerythronolide B synthase genes show how near is the realization of the idea of producing new chemical compounds by creating DNA information.

2

Production of proteins in the cell-free expression systems

100%

Szaflarski W., Sujka P., Nowicki M., Zabel M.

Biotechnologia

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2009

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issue 1

86-97

EN

Efficient protein synthesis has become a critical issue in recent biotechnology and functional protemic studies. Traditional expression of protein performed in host cells such as Escherichia coli or Saccharomyces cerevisiae is generally lengthy and costly. Cell-free protein synthesis is an attractive alternative offering simplicity and fast rate of the reaction as well as the generation of functional proteins that are difficult to obtain using in vivo systems. Furthermore, the open nature of these systems makes it amenable to manipulation allowing the investigations into the mechanism of protein synthesis itself and into the inhibition of that process by interfering molecules such as antibiotics. Here we review all the main classes of cell-free protein expression system and we emphasize their potency and recent applications in biotechnology.

3

Pneumolysin as a vaccine and drug target in the prevention and treatment of invasive pneumococcal disease

88%

Cockeran R., AndersonR., Feldman C.

Archivum Immunologiae et Therapiae Experimentalis

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2005

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vol. 53

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issue 3

189-198

EN

Streptococcus pneumoniae (the pneumococcus) remains one of the major human pathogens and one of the most common causes of community-acquired pneumonia, otitis media, sinusitis, and meningitis. Aside from the threats posed by emerging antibiotic resistance and infection with the human immunodeficiency virus, the mortality rate among those patients with severe pneumococcal disease who receive seemingly appropriate antimicrobial chemotherapy remains unacceptably high. Because of its involvement in the pathogenesis of invasive disease, pneumolysin, one of the best-characterized virulence factors of the pneumococcus, represents not only a potential vaccine target, but also a target for adjunctive therapy to antibiotics in patients with acute pneumococcal disease. In this paper we review the cytolytic and pro-inflammatory properties of pneumolysin and their involvement in sub-version of host defenses and extra-pulmonary dissemination of the pneumococcus, as well as strategies, both immunological and pharmacological, which may counter these harmful activities of the toxin.

4

Structural basis for the antibacterial activity of the 12-membered-ring mono-sugar macrolide methymycin

75%

Auerbach T., Mermershtain I., Bashan A., Davidovich C., Rozenberg H., Sherman D. H., Yonath A.

Biotechnologia

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2009

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issue 1

24-35

EN

The crystal structure of the complex of the large ribosomal subunit of the pathogen model Deinococcus radiodurans with the macrolide antibiotic methymycin, bearing a 12 membered macrolactone ring macrolide that contains a single amino sugar, shows that methymycin binds to the peptidyl transferase center (PTC) rather than to the high affinity macrolide binding pocket at the upper end of the ribosomal exit tunnel. This unexpected binding mode result in fairly efficient blockage of the 3'end of the A-site tRNA location, thus indicating the superiority of spatial-functional considerations over the formation of the typical high affinity macrolide interactions that due to the small size of methymycin could have led to incomplete blockage of the exit tunnel. Its binding involves rearrangements of several PTC nucleotides, some of which shown previously to be flexible. Comparisons between the binding modes of methymycin and other antibiotics are presented and discussed.

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From DNA sequence to antibiotic

Production of proteins in the cell-free expression systems

Pneumolysin as a vaccine and drug target in the prevention and treatment of invasive pneumococcal disease

Structural basis for the antibacterial activity of the 12-membered-ring mono-sugar macrolide methymycin