Antibiotics, biosynthesis polypeptide

Keating, T. A., and Walsh, C. T. (1999). Initiation, elongation, and termination strategies in polyketide and polypeptide antibiotic biosynthesis. Curr. Opin. Chem. Biol., 3, 598-606. 

Magnesium or lithium enolates of thiol carboxylic esters can be acylated with suitable reagents (c/ Volume 2, Part 1). Highly functionalized new derivatives are obtained. The example shown in equation (35)33,102 J5 closely related to the C-acylation of malonyl-CoA with acetyl-CoA, which plays an important role in the biosynthesis of polypeptides and fatty acids. (S)-4-Hydroxy-5-methyl-3-oxo-hexanoyl-L-leucine esters (41), 2-demethyl analogs of the Hip-Leu moiety of didemnin antibiotics, can be prepared via the 3-keto thiol carboxylic esters (40 equation 36). ° ... 

Type II polyketide synthases, also referred to as bacterial aromatic polyketide synthases (25) are involved in the biosynthesis of a number of clinically important bacterial aromatic polyketides products exhibiting antitumor or antibiotic activity, such as doxorubicin and oxytetracycline. As mentioned, type II synthases are evolutionarily and structurally related to type II FASs, which occurr as heteromultimeric complexes. In contrast to type I synthases however, where multiple catalytic sites occur within a given subunit, the polypeptides associated with type II synthase complexes are typically monofimctional and dissociable 20,30). 

Blasticidins pyrimidine antibiotics synthesized by Streptomyces griseochromogenes (see Nucleoside antibiotics). They inhibit the growth of fungi, e.g. the rice fungus, Piricularia oryzae, and a few bacteria. The antibiotic effect is due to suppression of polypeptide chain elongation during protein biosynthesis. 

Attention is directed to the inhibition of cell wall biosynthesis by endurac idin, a basic polypeptide, and by the phosphorus containing antibiotics moenomycin and... 

Mach, B., E. Reich, and E. L. Tatum Separation of the biosynthesis of the antibiotic polypeptide tyrocidine from protein biosynthesis. Proc. Natl. Acad. Sci. U.S. 50,... 

Uemura, I., J. W. Bodley, P. R. Adiga, and T. Winnick Effect of antibiotics and ribonuclease on polypeptide and protein biosynthesis in different strains of Bacillus brevis. Biochim. et Biophys. Acta 95, 86 (1965). 

Since edeine is a polypeptide of unusual amino acid composition, studies on the biosynthesis of this compound have been undertaken. Several studies on the mechanism of the formation of polypeptide antibiotics by intact cells of different B. brevis strains, and by cell-free systems, have been reported recently, but without full agreement as to whether or not these substances are S5mthesized by the same mechanism as are proteins (Okuda et al., 1964a Okuda et aL, 1964b Uemura et aL, 1963 Berg et al., 1965 Eikhom et al., 1964 Mach et al., 1963 Okuda et al., 1963 Yukioka et al., 1965). 

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