Blasticidin biosynthesis

There are two commercial fungicides, the antibiotics blasticidin S and kasugamycin, that act via the inhibition of protein biosynthesis (Figure 4.19). Blasticidin S is a fermentation product obtained from cultures of Streptomyces griseochromogenes, and has specific activity in the control of P. oryzae, similar to kasugamycin, a secondary metabolite of S. kasugaensis. However, much of the earlier work on mode of action was carried out using another antibiotic, cycloheximide. 

With the structures of aflastatin A (53) and B (N-demethyl aflastatin A, 54) secured, the structure of the related blasticidin A (52) was determined in a similar manner. Studies on the biosynthesis of aflastatin A... 

There are numerous examples of the inhibition of biosynthesis by fungicides. Some fungicidal secondary metabolites, like cyclohexi-mide and blasticidine, interfere with synthesis of peptide bonds at the ribosomal site (2). Another, kasugamycine, influences aminoacyl-t-RNA/ribosome interactions (3). Finally, another mechanism inhibiting protein biosynthesis is realized on the DNA/RNA- level by the... 

Blasticidin S (327) is an antifungal agent used against rice blast disease in Japan. It was isolated in 1958 from Streptomyces griseochromogenes [411] and the structure and absolute stereochemistry were elucidated by chemical means [412-415] and confirmed by X-ray spectroscopy [416,417]. The biosynthesis has also been determined [418,419]. 

The final stages in the biosynthesis of the peptidyl-nucleoside antifungal agent blasticidin S, produced by Streptomyces griseochromogenes, have been eluci-... 

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. 

Blasticidin S, 1 was isolated fiom Strefttottivces griseocltTomogcnes (1) as part of a major effort CO replace morcury-based compounds for the prevention of Pirit nlti arytue infection of rice plants in Japan (2). This fungus causes rice blast disease, a major rice pathogen in Japan and other parts of Asia. The structure and absolute stereochemistry of blast -cidirt S were determined by chemical degradation (3-6), and confirmed by x-ray diffraction (7,8). This work, as well as preliminary studies of blasticidin S biosynthesis, has been reviewed (9). 

Blasticidin 5 has been referred to variously as a peptidyl nucleoside, as an amino-acyl nucleoside, and as a 4 aminoacyl-4 deoxypyranosyIcytosine. In this chapter it will be referred to by the first of these. We will focus on the biosynthesis of blasticidin S and its cometabolites, the mechanism of action of blasticidin S, and resistance exhibited by microorganisms, plants, and animals. 

Yonehara H. Blasticidin S Ptopertics. biosynthesis, and feimentation. Vandainme EJ. ed. Biotechnology of Industrial Antibiotics. New York Marcel Dekker. 1984 651-663. 

Seto H, Yonehara H. Studies on the biosynthesis of blasticidin S. VII. Isolation of demeihyl-blasticidin S. j Antibiot 1977 30 1022-1024. 

Prabhakaran PC, Woo NT, Yorgey P, Gould SJ. Biosynthesis of blasticidin S from L-Ct-argi-trine. Stereochemistry in the arginine-2,3-aminomutase leaciion. J Am Chem Soc 1988 ... 

Guo J, Could SJ. Biosynthesis of blasticidin S. Cell-free demansnadon of N-methylation as the last step. Btootg Med Chem Lett 1991 1 497-500. 

Could SJ, Tann CH, Prabhakaran PC, Hillis LR. [2,3,4.6.6- Hj)-l>-Glucose as a general probe for sugar transformations in microbial metabolism A q>[icati(Hi to the biosynthesis of sarubicin A, blasticidin S, and streptothricin F. Biooig Qiem 1988 16 258-271. 

Gould SJ, Guo J, Dejesus K, Geitmann A. Nucleoside intermediates in blasticidin S biosynthesis identified by the in vivo use of enzyme inhibitors. Can J Chem 1994 72 6-11. 

---