Antimicrobial enzymes

NPs are used in the preparation of bio-nanocompositesmainly for two reasons, to create tortuous path in order to improve the barrier properties (as filler) and to induce various desired effects (as an additive) such as immobilization of enzymes, antimicrobial activity, biosensing, and so on. Varions types of NPs, including clay and silicates, Cellulose based nano-reinforcements, CNTs, Silica, Starch nanocrystals, chitin and chitosan NPs, and metal oxides, are presently nsed to enhance the biopolymer performance. 

Antibiotic and Antimicrobial Drugs. The antimicrobial agents (119) flumequiae (160) and (161), and methylflumequiae (S-25930) (162) and (163) effectively eliminate a number of microbial pathogens via inhibition of the topoisomerase II enzyme of c-DNA containing bacteria (120) (see... 

A number of important papers could not be cited in this chapter, due to the length limitations and the specific target of the chapter. For example, the antimicrobial activity of chitosans [349], the chitinolytic enzymes, the preparation of cosmetics, and the occurrence of chitin in fungi [350] are some of the subjects not dealt with specifically here, notwithstanding their importance. 

The antimicrobial action of ethambutol, like that of isoniazid, is specific for mycobacteria, suggesting a target in the unique components of the mycobacterial cell wall. Cells treated with ethambutol accumulate an isoprenoid intermediate, decaprenyl-arabinose which is the source ofarabinose in the arabinogalactan polymer. This suggests that ethambutol blocks assembly of the arabinogalactan through inhibition of an arabinosyl transferase enzyme. 

Although a few mechanisms have so far been proposed to explain the antimicrobial properties exhibited by proanthocyanidins (e.g., inhibition of extracellular enzymes) [86], Jones et al. [83] postulated that their ability to bind bacterial cell coat polymers and their abihty to inhibit cell-associated proteolysis might be considered responsible for the observed activity (Table 1). Accordingly, despite the formation of complexes with cell coat polymers, proanthocyanidins penetrated to the cell wall in sufficient concentration to react with one or more ultra-structural components and to selectively inhibit cell wall synthesis. Decreased proteolysis in these strains may also reflect a reduction of the export of proteases from the cell in the presence of proanthocyanidins [83]. 

Angiotensin converting enzyme inhibitors, azathioprine, mer-captopurine, mesalamine, sulfasalazine, sulfonamide antimicrobials, and tetracyclines... 

Figure 4 Stabilized bromine antimicrobials are produced by eosinophils, a type of mammalian white blood cell. Bacteria are captured by phagocytosis and contained intracellularly within vesicles called phagosomes. Granules release cationic surfactants, lytic enzymes, and eosinophil peroxidase into the phagosome in a process known as degranulation. Eosinophil peroxidase, an enzyme that is structurally similar to the bromoperoxidases found in seaweed (Figure I), selectively catalyzes oxidation of bromide to hypobromite by reducing hydrogen peroxide to water. The hypobromite immediately reacts with nitrogenous stabilizers such as aminoethanesulfonic acid (taurine) to form more effective and less toxic antimicrobial agents.

Jensen, S.E., Elder, K.J., Aidoo, K.A. and Paradkar, A.S., (2000) Enzymes catalyzing the early steps of clavulanic acid biosynthesis are encoded by two sets of paralogous genes in Streptomyces clavuligerus. Antimicrobial Agents and Chemotherapy, 44, 720-726. 

In another study, the carrier protein was replaced by an enzyme compatible solid-phase resin (PEGA), and enzyme-catalyzed cyclization was used to probe substrate specificity. This study demonstrated also that oxo-esters are tolerated as substrates for TE domains, and then-preparation in library format served as an excellent tool for substrate specificity studies, as well as for preparation of cyclized peptides. Figure 13.11 shows how the TycA TE showed selectivity for only residues 1 and 9 (colored in red), and changes at all other residues were tolerated [42]. Hydrogen bonding interactions are shown in green. Several compounds made from this series were shown to demonstrate improved therapeutic indices (with respect to hemolysis) while retaining antimicrobial activity. 

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