Research Items

Abstract

Antibiotics from Aspergillus fumigatus: Identity of Helvolic Acid and Fumigacin THE mould Aspergillus fumigatus gives rise to no fewer than four crystalline metabolic products possessing antibacterial activity. Of these, two compounds, fumigatin and spinulosin, have been definitely characterized and identified (Anslow and Rais-trick, Biochem. J., 32, 687 and 2288; 1938; Oxford and Raistrick, Chem. and Ind., 61, 128; 1942). They are, in fact, closely related and have the constitutions 3-hydroxy-4-methoxy-2: 5-toluquinone and 3: 6-di-hydroxy-4-methoxy-2: 5-toluquinone, respectively. A third product, helvolic acid, m.p. 204·5–212°, was isolated from A. fumigatus mut. helvola and described by Chain, Florey, Jennings and Williams (Brit. J. Exp. Path., 24, 108; 1943). It is nitrogen free and has the empirical formula C32H44O8 (deduced from ultimate analysis and X-ray mol. wt. data) and forms a monomethyl ester. Nothing further is known as to its constitution, but the substance is stated to be relatively non-toxic to animals, although active against Gram-positive organisms, for example, Staphylococcus aureus at 1: 80,000, complete inhibition. Prior to this discovery another antibiotic from A. fumigatus was described by Waksman, Horning and Spencer (Science, 96, 202; 1942; J. Bact., 45, 233; 1943) and was given the name fumigacin. It was stated to have a melting point of 185–187°, to contain 3·7 per cent of nitrogen and to be active against Gram-positive bacteria. In a forthcoming issue of Science, Waksman states that Menzel, Winter-sterner and Hoogerheide have demonstrated that fumigacin as prepared by Waksman contains s 20 per cent of gliotoxin, C13H14N2O4S2, an antibiotic from Gliocladium fimbriatum and toxic to animals (Johnson, Bruce and Dutcher, J. Amer. Chem. Soc., 65, 2005; 1943). On removal of the gliotoxin fraction, the purified fumigacin was found to be identical with helvolic acid in chemical composition, antibacterial activity and in vivo activity. The antibacterial metabolic products of A. fumigatus so far identified are therefore fumigatin, spinulosin, helvolic acid (or purified fumigacin) and gliotoxin.