Naslov
Non-ribosomal peptide biosynthetic systems

Autori
Pavela-Vrančič, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
1st Croatian Congress on Molecular Life Sciences with International Participation, Book of Abstracts / Dumić, Jerka et al. - Zagreb : Farmaceutsko-biokemijski fakultet Sveučilišta u Zagrebu, 2002

Skup
1st Croatian Congress on Molecular Life Sciences with International Participation

Mjesto i datum
Opatija, Hrvatska, 09.06.2002. - 13.06.2002

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Sažetak
The increasing number of pathogenic organisms developing resistance to traditional therapy requires novel concepts for the generation of pharmacologically useful drugs. A wide variety of natural peptides, peptidolactones, and depsipeptides, are synthesised non-ribosomally with the aid of multifunctional peptide synthetases. Several hundred compounds of numerous structural diversity are known to exhibit a broad spectrum of useful biological properties qualifying them for biotechnological and medical uses as antibiotics (gramicidin, tyrocidine, penicilline), immunomodulators (cyclosporin), extracellular surfactants (surfactin) or siderophores (enterobactin, ferrichrome). Contrary to the ribosomal system, in which coupling of amino acids proceeds by virtue of mRNA-directed elongation, the non-ribosomal process is determined exclusively by the protein template. The activation of the carboxyl substrate proceeds by a two step reaction mechanism: an aminoacyl adenylate-enzyme complex is formed at the expense of ATP, followed by transfer of the activated acyl moiety to the sulfhydryl group of the covalently bound 4′-phosphopantetheine cofactor under formation of a thioacyl intermediate. At this stage the substrate may undergo modification, epimerization or N-methylation. Thioesterified acyl moieties are integrated into the peptide product through step-by-step elongation by a series of transpeptidation reactions. The biosynthetic process is terminated by hydrolysis, cyclization or terminal modification. The modular organisation of peptide synthetases opens up prospects for the generation of highly specialised peptide products by combining amino acid introducing elements, or modules, into new peptide forming systems. Prerequisites for a successful design of new peptide products are a better understanding of the structure-function relationship within the polypeptide chain, the mechanism of substrate selection, channelling of covalently bound intermediates to the adjacent module, their condensation and the principles of regulation in the biosynthetic process. This knowledge should be helpful for the rational design of bioactive peptides and for exploring the potential of protein templates in combinatorial synthesis for the generation of structural and consequently functional diversity.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA