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Nonribosomal peptide synthetases (NRPSs) are multimodular enzymes that produce a wide range of bioactive peptides, such as siderophores, toxins, and antibacterial and insecticidal agents. NRPSs are dynamic proteins characterized by extensive interdomain communications as a consequence of their assembly-line mode of synthesis. Hence, crystal structures of multidomain fragments of NRPSs have aided in elucidating crucial interdomain interactions that occur during different steps of the NRPS catalytic cycle. One crucial yet unexplored interaction is that between the reductase (R) domain and the peptide carrier protein (PCP) domain. R domains are members of the short-chain dehydrogenase/reductase family and function as termination domains that catalyze the reductive release of the final peptide product from the terminal PCP domain of the NRPS. Here, we report the crystal structure of an archaeal NRPS PCP-R didomain construct. This is the first NRPS R domain structure to be determined together with the upstream PCP domain and is also the first structure of an archaeal NRPS to be reported. The structure reveals that a novel helix-turn-helix motif, found in NRPS R domains but not in other shortchain dehydrogenase/reductase family members, plays a major role in the interface between the PCP and R domains. The information derived from the described PCP-R interface will aid in gaining further mechanistic insights into the peptide termination reaction catalyzed by the R domain and may have implications in engineering NRPSs to synthesize novel peptide products. [ABSTRACT FROM AUTHOR]

Abstract: Burkholderia glumae, a bacterial pathogen on rice, produced compounds in liquid culture that, in agar diffusion assays, gave strong inhibitory action against Erwinia amylovora, the bacterium responsible for fire blight disease of apple and pear trees. Products were isolated from culture medium by cation exchange and then purified by bioassay-guided chromatographic methods. Two major products were obtained, one of which was not active when fully purified. Each product showed a single ninhydrin-staining spot on TLC and a single HPLC peak. The non-active product was deduced from NMR, MS, and chemical data, to be the tripeptide l-alanyl-l-homoserinyl-l-aspartate. The NMR data for the active product demonstrated that it contained the same tripeptide, but functionalised at the β-carboxyl of the C-terminal aspartate, by a moiety that provided an additional 98 mass units to the parent tripeptide. Various data led to the interpretation that this moiety was a highly unusual oxygenated pyrazole structure, and thus the bioactive product was deduced to be 3-[l-alanyl-l-homoserinyl-l-aspartyl-β-carboxy]-4-hydroxy-5-oxopyrazole. This compound was found to inhibit the growth of a number of different bacterial species. [Copyright &y& Elsevier]

The article presents a safer method to synthesize the sulfonamide drug sulfathiazole for undergraduate classes. Key features of the experiment include the total exclusion of pyridine and a simplified procedure for converting the intermediate p-acetamidobenzenesulfonamide to the final product by acid hydrolysis. Antibacterial testing of the purified product were carried out against Escherichia coli.

[Display omitted] Octapeptin B5 peptides containing a novel fatty acids have been found to have enhanced antibacterial activity against Staphylococcus aureus and also have an excellent safety profile. Cyclic lipopeptides such as the polymyxins and battacin are potent antibacterial agents. It has been shown that truncated, non-linear, versions of these agents (e.g. octapeptin B5) can retain the activity of the more complex cyclic compounds. In this work the synthesis of Octapeptin B5 peptides containing a range of novel fatty acids is reported. Many of these lipopeptides have been found to have enhanced antibacterial activity against Staphylococcus aureus compared to Octapeptin B5 whilst also having an excellent safety profile in haemolytic and cytotoxicity assays. [ABSTRACT FROM AUTHOR]

Synthesis of 6- O -(3-alkylamino-2-hydroxypropyl) derivatives of chitosan was achieved using a four-step strategy of N -protection, O -epoxide addition, epoxide ring opening using an amine and N -deprotection. Benzaldehyde and phthalic anhydride were used for the N -protection step, producing N -benzylidene and N -phthaloyl protected derivatives, respectively, resulting in two corresponding final 6- O -(3-alkylamino-2-hydroxypropyl) derivative series, BD1-BD6 and PD1-PD14. All the compounds were characterized using FTIR, XPS and PXRD studies and tested for antibacterial efficacy. The phthalimide protection strategy was found to be easier to apply and effective in terms of the synthetic process and improvement in antibacterial activity. Amongst the newly synthesized compounds, PD13 (6- O -(3-(2-(N , N -dimethylamino)ethylamino)-2-hydroxypropyl)chitosan) was the most active with eight times greater activity compared to the unmodified chitosan and, PD7 6- O -(3-(3-(N -(3-aminopropyl)propane-1,3-diamino)propylamino)-2-hydroxypropyl)chitosan) having a four-fold activity than chitosan, was found to be the second most potent derivative. This work has produced new chitosan derivatives those are more potent than chitosan itself and show promise in antimicrobial applications. • New 6- O -(3-alkylamino-2-hydroxypropyl) derivatives of chitosan were synthesized. • N -benzylidene and N -phthaloyl protection/deprotection strategies were compared. • Antibacterial testing was achieved under neutral pH conditions without using solvents. • Compounds with eight-fold and four-fold greater activity against S. aureus than chitosan were developed. [ABSTRACT FROM AUTHOR]