Streptomyces hydroscopicus

Although it is not chemically related to cyclosporine, tacrolimus (6.7) has a similar mechanism of action. Tacrolimus is an immunosuppressant macrolide antibiotic derived from Streptomyces tsukubaenis. Like cyclosporine, tacrolimus inhibits the same cytoplasmic phosphatase, calcineurin, which catalyzes the activation of a T-cell-specific transcription factor (NF-AT) involved in the biosyntheses of interleukins such as IL-2. Sirolimus (6.8) is a natural product produced by Streptomyces hydroscopicus, it blocks the ability of T cells to respond to cytokines. 

Several years after publishing their results the Ghaderi group returned to these cyclopeptides, prompted by the discovery that antibacterial compounds isolated from Streptomyces hydroscopicus, known as mannopeptimycins, were also based on... 

Finally, we should mention a series of synthetic approaches to L-pyrophosphino-tricine 144, a cyclic analogue of L-phosphinotricine, and its Ala-Ala peptide 145, a cyclic analogue of bialaphos (tripeptide of L-phosphinotricine produced in nature by Streptomyces hydroscopicus) [186], As the final step, the procedures comprised enzyme-catalysed hydrolysis and resolution of the racemic mixtures formed into optical antipodes by a-chymotripsin. Both 1,2-azaphospholane 144 and its tripeptide 145 exhibit antitumour activity. Moreover, tripeptide 145 displayed a greater bactericidal activity than the antibiotic bialaphos. 

Trichostatin A (38a) is a ( , )-A -hydroxy-7-oxo-2,4-heptadienamide isolated from some strains of Streptomyces hydroscopicus and is an antifungal antibiotic [65] as well as a potent inhibitor of mammalian histone deacetylase used in cancer chemoprevention. Two other metabolites with similar biological activity have also been isolated trichostatin B (38b), which is the corresponding ferric chelate [65] and trichostatin C (38c), a glucopyranosyl derivative [66]. 

Maridomycin III, in which both ester groups are propionyl derivatives, is the principal component of the maridomycin complex elaborated by a valine resistant mutant of Streptomyces hydroscopicus (the six components differ depending on whether acetyl, propionyl, or isovaleryl ester groups are present). The... 

Figure 5.37. Dependence of kinetic parameters and 2 the model of filamentous growth (see Equ. 5.110) on glucose concentration s in case of chemostat culture of Streptomyces hydroscopicus. (From Bergter, 1978.)...

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