Mycobactins

Mikes and Turkova have given a classification of naturally occurring hydroxamic acids in terms of their biological function or activity. They have distinguished (a) growth factors, e.g., ferri-chromes, mycobactin, and ferrioxamines, ferrichrysins, ferrirubins, etc. (6) antibiotics, e.g, aspergillic acid, mycelianamide, albomycin, nocardamine and (c) microbial pigments such as pulcherrimin. 

Francis et and Snow have isolated from Mycobacterium phlei and M. tuberculosis two series of growth factors for M. johnei, containing the mycobactins P (12) and T (13), respectively. 

Mild alkaline hydrolysis cleaved the molecules as shown by the dotted line to give the carboxylic cobactic acids and the neutral cobactins. Acidic hydrolysis resulted in complex fission of the molecule into smaller fragments. No synthetic work in the mycobactin series has been reported, but the structures are based on very extensive degradations. 

DMD was employed to oxidize /Va-carbobenzyloxy (Cbz)-L-lysine tert-butyl ester to the corresponding lysine-based dimethyl nitrone, an important synthetic intermediate of the mycobactins (78). 

Exochelins (322,323) are peptidic siderophores imm Mycobacterium spp. (see also below mycobactins). Exochelin MS (16) from M. smegmatis comprises (3-Ala and three W -OHOm units, which are linked by their atoms to acyl groups thus forming hydroxamic acids. 

Transvalencin Z (245a) from Nocardia transvalensis could be a precursor or side product of mycobactin biosynthesis, possibly acquired from a vagabonding gene. It comprises the left part of the serine/salicylic acid based molecules (Table 5 R" = = H) and ends with A/ -formyl-Lys (R = H, no iV-hydroxy group). The... 

Iron uptake of Mycobacterium smegmatis involving mycobactin S was studied... 

When DHB is bound to serine or threonine cyclization may occur resulting in an oxazoline ring cf. above anachelin, Sect. 2.3, and mycobactins, Sect. 2.8). It has been discussed whether the oxazoline nitrogen atom may act as a ligand site (see below, (505)). This would explain why DHB is replaced by a salicylic acid residue in some cases. 

Barklay R, Ewing DF, Ratledge C (1985) Isolation, Identification, and Structural Analysis of the Mycobactins of Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium scrofulaceum, and Mycobacterium paratuberculosis. J Bacteriol 164 896... 

McCullough WG, Merkal RS (1982) Stmcture of Mycobactin J. Curr Microbiol 7 337... 

Ratledge C, Marshall BJ (1972) Iron Transport in Mycobacterium smegmatis the Role of Mycobactin. Biochim Biophys Acta 279 58... 

Snow GA (1965) The Structure of Mycobactin P, a Growth Factor for Mycobacterium johnei, and the Significance of its Iron Complex. Biochem J 94 160... 

Snow GA (1965) Isolation and Structure of Mycobactin T, a Growth Factor from Mycobacterium tuberculosis. Biochem J 97 166... 

Snow GA (1970) Mycobactins Iron-chelating Growth Factors from Mycobacteria. Bacter-iol Rev 34 99... 

Snow GA, White AJ (1969) Chemical and Biological Properties of Mycobactins Isolated from Various Mycobacteria. Biochem J 115 1031... 

White AJ, Snow GA (1969) Isolation of Mycobactins from Various Mycobacteria. The Properties of Mycobactins S and H. Biochem J 111 785... 

Pharmacology Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis. It inhibits the onset of bacterial resistance to streptomycin and isoniazid. The mechanism of action has been postulated to be inhibition of folic acid synthesis (but without potentiation with antifolic compounds) or inhibition of synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis. 

Bacterial siderophores are another class of widespread toxins produced by bacteria. On land, mycobactins and exophilins are the best-known representatives. Those found in the sea, aquachelins, marinobactins, anguibactin, vulnibactin, and aerobactin (Table 12.3.1) are amphiphilic. This is a property that has received great attention for drug delivery problems and in relation to recognition processes (Testa 2000), devising efBcient algorithms for computer calculation (Fisher 2000). 

The possible role of the mycobactins in the storage of iron in the mycobacteria has been noted. Of greater significance is the identification of ferritin-like molecules in some bacteria. The cytochrome 6557.5 from Azotobacter vinelandii, known to be associated with large amounts of iron, is now known to be a ferritin, with an iron content of 13-20% and an electron-dense core of... 

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