Streptomyces hygroscopicus var

Pimecrolimus (SDZ ASM 981, Elidel) is another recently approved macrolide immunosuppressant that acts by inhibiting calcineurin and blocking the release of proinflammatory cytokines from T lymphocytes. The parent compound, ascomycin, was originally isolated from Streptomyces hygroscopicus var ascomyceticus. Like tacrolimus, pimecrolimus is approved for the topical treatment of moderate to severe atopic dermatitis that is refractory to other therapies. Transient local irritation is a common side effect. 

Validamycin A is the only commercial fungicide active against this target (Figure 4.9). The compound is an aminoglycosidic pseudosaccharide and is a secondary metabolite produced in the fermentation of Streptomyces hygroscopicus var. limoneus. Validamycin A was introduced by Takeda Chemical Industries Ltd. for the control of Basidiomy-cetes and Corticiaceae, especially sheath blight, Rhizoctonia solani, in rice. 

The first evidence for aminocarbapyranoses occurring in Nature dates back to early 70s with the discovery of validamine 202 (Chart 3), a carbasugar constituent of Validamycins, an antibiotic complex which shows growth inhibition activity against bacterial diseases of rice plants [50]. Shortly after, validamine 202, along with valiolamine 203 and valienamine 204, (Chart 3), were isolated from the fermentation broth of Streptomyces hygroscopicus var. limoneus [50],... 

Valiolamine (89), an aminocyclitol produced by Streptomyces hygroscopicus var. limoneus, is a potent inhibitor of pig intestinal maltase and sucrase, with IC50 values of 2.2 and 0.049 pM, respectively [107]. Numerous iV-substituted valiolamine derivatives were synthesized to enhance its a-glucosidase inhibitory activity in vitro and the very simple derivative voglibose (90), which is obtained by reductive amination of valiolamine with dihydroxyacetone, was selected as the potential oral antidiabetic agent [108]. Its IC50 values toward maltase and sucrase were 0.015 and 0.0046 pM, respectively. Voglibose (the brand name Basen) has been commercially available for the treatment of type 2 diabetes in Japan since 1994. 

Ytinsten, Ohkuma, and Ishii isolated, from the fermentation broth of Streptomyces hygroscopicus var. angustmyceiicus, an antibiotic substance which they named Angustmycin. They were able to separate Angustmycin into three components—adenine and two heretofore-unknown purine nucleosides, Angustmycin A (29) and Angustmycin C (30). Both nucleosides were hydrolyzed to adenine and were shown, by spectral data, to be... 

Streptomyces hygroscopicus var. geldanus and shows antibiotic activity against protozoa [206]. From the same Streptomyces strain, AM-3672, herbimycin A (124) [207], B (125) [208] and C (126) have been isolated [209]. They exhibit herbicidal and antiviral activity and are able to reverse the characteristics of oncogene expression [120]. Herbimycin A (124) has been shown to have a potent antiangiogenic activity [211]. This latter biological activity distinguishes the benzoquinoid ansamycins from their benzenoid [212] and naphthoquinoid [213] ansamycin relatives. 

Wu, K., Chung, L., Revill, W. P., Katz, L., and Reeves, C. D. (2000). The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units. Gene 251, 81-90. 

As described above, the first benzenoid ansa macrolides were isolated from a higher plant. On the other hand, the first ansa macrolide from a microorganism was isolated from the culture filtrate of Streptomyces hygroscopicus var. geldanus and named as geldanamycin (85) [137]. Geldanamycin (85) showed an inhibitory effect on the growth and multiplication of protozoa and possessed potent cytocidal activities in vitro. 

A group of more than 20 naturally occurring macro-lide antibiotics from Streptomyces hygroscopicus var. aureolacrimosus with antiparasitic, insecticidal, and acaricidal activities. Common structural features are the differently substituted, 16-membered lactone ring and a spiroketal unit. In terms of structure and activity, the M. are closely related with the avermectins. Examples of this class of compounds are M. D (C33H48O7, Mr 556.74, needles, mp. 186-188 °C), M. E (C34H52O7, Mr 572.78, amorphous) and M. (C3,H4205, Mr 494.67) . 

C,4H25N09 351.353 Isol. from Streptomyces hygroscopicus var. limoneus. Amorph. solid + H2O. Sol. H2O, MeOH, DMSO poorly sol. EtOH, Mc2CO, hexane. [a]o +118.6(c, 1 inH20). 

Geldanamycin Streptomyces hygroscopicus var. geldanus var. nova Maytansine Maytenus ovatus Loes... 

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