Biochemistry of the Ustilaginales: Vii. Antibiotic Activity of Ustilagic Acid

Abstract

The antibiotic activity of Ustilago zeae (PRL 119) cultures is associated mainly with the culture solids and it has been shown that a mixture of glucolipids, called ustilagic acid and produced in good yields by the fungus, is responsible for part, if not all, of the observed activity. The antibiotic activity of ustilagic acid corresponds to that originally attributed to ustizeain B and therefore these two are considered to be identical. All samples of ustilagic acid obtained showed antibiotic activity and it has not been possible by paper chromatography to separate an active principle from the acid. Recrystallization of ustilagic acid did not alter its antibiotic properties. Alkaline hydrolysis of the acid destroyed its activity. Heating the culture mixture for up to an hour at temperatures less than 100° C. did not alter materially the antibiotic properties of the mixture or of the acid extracted therefrom. The antifungal spectrum is broad and the antibacterial spectrum includes more Gram-positive than Gram-negative organisms. Preliminary tests with rats indicated that ustilagic acid is nontoxic when administered orally up to at least 5% of the diet, and with mice, orally up to at least 1% of the diet or intraperitoneally in amounts up to 1.5 gm. per kgm. of body weight.

Activation of the Ustilagic Acid Biosynthesis Gene Cluster in Ustilago maydis by the C 2 H 2 Zinc Finger Transcription Factor Rua1

“…The secreted cellobiose lipid UA has broad antibacterial and antifungal spectra (11). Coinoculation of wild-type U. maydis cells effectively prevents infection of tomato leaves by Botrytis cinerea, the causal agent of gray mold disease.…”

“…In addition, U. maydis produces the cellobiose lipid ustilagic acid (UA) (see Fig. 2A), which has broad antibacterial and antifungal spectra (11). The enzymes involved in biosynthesis of these glycolipids are in both cases encoded by genes found at adjacent locations on the chromosome.…”

Beta Hydroxylation of Glycolipids from Ustilago maydis and Pseudozyma flocculosa by an NADPH-Dependent β-Hydroxylase

“…Ustilago maydis (de Candolle) Corda and Pseudozyma flocculosa (Traquair, Shaw & Jarvis) Boekhout & Traquair are two basidiomycete fungi that produce very similar glycolipids with antibiotic activities (8,17,18). While U. maydis is a phytopathogenic fungus that infects corn plants and causes smut diseases, P. flocculosa is a natural inhabitant of the phyllosphere that has been described as a biocontrol agent with particular activity against powdery-mildew pathogens (1,19).…”

“…Ustilagic acid (UA), the glycolipid produced by U. maydis, is a mixture of four different derivatives consisting of cellobiose o-glycosidically linked to 15,16-dihydroxypalmitic or 2,15,16-trihydroxypalmitic acid. In addition, the UA molecule is acetylated and esterified with a short-chain ␤-hydroxy fatty acid with a length of either C 6 or C 8 . In contrast to UA, flocculosin, which is produced by P. flocculosa, has only one known isomer consisting of 3,15,16-trihydroxypalmitic acid linked to the cellobiose moiety.…”

Biochemistry of the Ustilaginales: Viii. The Structures and Configurations of the Ustilic Acids

“…The new antibiotic (8) termed ustilagic acid was shown (15) to be a illixture of closely related, partially acylated D-glucolipides. Alkaline hydrolysis of ustilagic acid yielded an anlorphous substance designated gl~~coustilic acid and removal of the glucose residues in the latter material yielded a crystalline substance termed ustilic acid (15).…”