Fattiviracins, Antiviral Antibiotics Produced by an Actinomycete

Abstract

In 1995, we discovered new antiherpetic antibiotics, called fattiviracins. The producing organism was classified as a strain belonging to Streptomyces microflavus. The strain produced at least 13 fattiviracin derivatives (FV-1 to FV-13). Fattiviracins were obtained as a white amorphous powder, and their molecular weights are in the range of 1400 to 1500. They are readily soluble in water, methanol, pyridine and DMSO, but insoluble in other organic solvents. Fattiviracins have macrocyclic diesters formed by the binding of two trihydroxy fatty acids and two D-glucose residues in the molecule, and they can be divided into 5 families, according to the length of fatty acid moiety. Fattiviracins have a potent activity against enveloped DNA viruses such as the herpes family, HSV-1 and VZV and enveloped RNA viruses such as influenza A and B viruses, and three strains of HIV-1, in the order of a few μg/ml of EC50. The biosynthetic pathway of fattiviracins is also becoming clearer. Using bacitracin-resistant strains, enhanced and astringent production of fattiviracin was recognized: fattiviracin FV-13, having the longest fatty acid chains in the molecule was dramatically enhanced by a C55-isoprenyl phosphate metabolism.