Iturine

Iturins are a group of fungicidal cyclic lipopeptides produced by Bacillus subtilis m m m All members of this group are cyclic octapeptides with seven a-amino acids and a unique 13-amino fatty acid homologue of iturinic acid. The predominant iturin-A isomer, A2, contains the n-C14-isomer of iturinic acid (Itu) (Scheme 8). The synthesis of the molecule can be divided into two steps with the first stage consisting of the assembly of the linear octapeptide on solid phase followed by the backbone cyclization in solution. 

The synthesis of the linear octapeptide was performed applying Fmoc/tBu chemistry and starting from 0.82 g (0.39 mmol-g-1, 0.32 mmol) of Fmoc-Ser(tBu)-HMPAA-resin (Millipore). Iturinic acid was coupled as the jV-Boc derivative. After deprotection and cleavage with TFA/H20 (95 5), the product was purified by preparative RP-HPLC yield 37 mg (74%). 

Trischman, J.A. Jensen, P.R. Fenical, W. (1994B)Halobacillin b a cytotoxic cyclic acylpeptide of the iturin class produced by a marine Bacillus. Tetrahedron Lett., 35, 5571-4. 

Another cyclic peptide, halobacillin, was isolated from a marine-derived Bacillus sp. isolated from a deep-sea sediment core.31 Halobacillin (Structure 18.21) was only produced in sea-water-based media and is similar in structure to the surfactins and iturins. Interestingly, the compound exhibits cytotoxicity against the human colon tumor cell fine HCT-116 but lacks the antibacterial activity associated with surfactin. 

Three new cytotoxic cyclopeptides, mixirins A 85, B 86, and C 87, of iturin class were isolated from marine bacterium Bacillus sp. These three compounds inhibited the growth of human colon tumor cells (HCT-116) with IC50 of 0.68, 1.6, 1.3 pg mL respectively. Solid-phase synthesis of the mixirins were also reported. ... 

Mycosubtilins were isolated by Peypoux et al. in 1976 as antifungal metabolites from B. subtil is. The constituent amino acids of mycosubtilin D are the same as those of iturin A, but the peptide sequences differ(Fig. 

Mizumoto, S., Hirai, M., and Shoda, M. (2006). Production of lipopeptide antibiotic iturin A using soybean curd residue cultivated with Bacillus subtilis in solid-state fermentation. Appl. Microbiol. Biotechnol. 72, 869-875. 

Iturins, a family of antifungal peptides produced by various strains of Bacillus suh-tilis. The iturins comprise small cyclic pep-tidolipids characterized by a lipid-soluble -amino acid linked to a peptide containing D- and L-amino acids [F. Peypoux et al.. Tetrahedron 1973, 29, 3455 M. Klich et al., Mycopathology 1991, 226, 77]. 

R 345 M. Blaut, L. Schoefer and A. Braune, Transformation of Flavonoids by Intestinal Microorganisms , Int. J. Vitam. Nutr. Res., 2003,73,79 R 346 J. -M. Bonmatin, O. Laprevote and F. Peypoux, Diversity among Microbial Cyclic Lipopeptides Iturins and Surfactins. Activity - Structure Relationships to Design New Bioactive Agents , Comb. Chem. High T. Scr., 2003,6, 541... 

Phister, T. G., O Sulhvan, D. J., McKay, L. L. (2004). Identification of bacilysin, chlorote-taine, and iturin a produced by Bacillus sp. strain CS93 isolated from pozol, a Mexican fermented maize dough. Applied and Environmental Microbiology, 70, 631-634. 

B. suhtilis Rapeseed meal containing protein (38.87%), total nitrogen (62.19mg/g), total phosphorus (19.19mg/g), carbohydrates (by-product from edible oil production) Iturin A and poly-y-glutamic acid 89... 

Yao D, Ji Z.Wang C, Qi G, Zhang L, Ma X, et al. Co-producing iturin A and poly-y-glutamic acid from rapeseed meal under solid state fermentation by the newly isolated Bacillus subtilis strain 3-10. World J Microbiol Biotechnol 2012 1—7. 

A wide variety of microorganisms also produce many kinds of surface-active lipoproteins or lipopeptides [63]. Mostly they exhibit the typical amphiphilic character and are generally extracellular. Representative of such surface-active lipopeptides is surfactin produced by Bacillus subtilis. It is composed of a heptapeptide cycle closed by a C14.15 P-hydroxy fatty acid that forms a lactone ring system (Fig. 15) [64]. This structure resembles those of iturins, another class of lipopeptides also produced by Bacillus subtilis [65]. 

Surfactin is a biosurfactant with a high industrial and commercial potential because of its superb surface and interfacial activity and because it has a diversity of bioactive properties. Surfactin forms large micelles at a very low concentration and the cmc is of the order of 10 M [66]. The bioactivities of surfactin include inhibition of blood clotting [67], hemolytic activity [68], channel formation in membranes [69], synergistic antifungal activity when combined with iturins, antibiotic activity [70], antitumor [71], and anti-HIV effects [72]. 

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