Studies on bioactive metabolites produced by pathogenic Nocardia

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During our studies on the toxic substances from clinically isolated pathogenic Nocardia, a newisolate idantificed as Nocardia otitidiscaviarum (from cutaneous nocardiosis) was found to produce a toxic substance calaled HS-6 which had strong in vitro as toxicity. Our further studies revealed that HS-6 ahows interesting biological activities such as accmulation of triglyceride in the liver. these results prompted us to isolate new bioactive substances includ-ing toxic ones from pathogenic Nocardia. Our screening studies could select 5 strains of phthoge-nic Nocardia as producers of bioactive substance(s). Isolation studies on bioactive substances from the selected phthogenic Nocardia resulted in an isolation of a new anthracyline compound (SO-075R1) from the mycelium of IFM-075 strain, which was identificed as Nocardia brasiliensis. It was not so toxic to cultured cells, showing ED^<50> value of 50 mug/ml against Vero cells. Itwas also active aginst gram-positive bacteria, but not active against gram-megative bacteria., Although it showed no antitumor activiteis, it showed antiviral activity against DNA virus such as HSV.Detail studies on other biological activities are conducted. We also isolated three minor components, disignated M-3, M-4 and M-13-1 from N.Brasiliensis IFM 075. The structural studies showed that they are new reduced anthracycline related compounds. Studies on biological acti-vities are now in progress. Biosynthetic studies on the compounds suggested that M-3, M-4 and M-13-1 might be derived by bioreduction of SO-075R1 or its anthracyclinone. We had reprted that phthogenic Nocardia showed species-specific resistant patterns. During our studies on the mechanisms of the resistance, we found interesting inactivation mechanisms of the antibiotics by the Nocardia. These include phosphorylation and glycosylation of rifampicin, and glycosylation, phosphorylation, reduction and transacylation of macrolide antibioitcs. Throughtout these studies, we repo