Biotransformation of pseudolaric acid B by Chaetomium globosum

Pseudolaric acid B (1) is a natural product with potent antifungal activity. We discovered that pseudolaric acid B did not kill but only suppress the growth of the filamentous fungus Chaetomium globosum. It was proposed that pseudolaric acid B was converted to metabolites with decreased antifungal activities. In this study, a scaled-up biotransformation of pseudolaric acid B by C. globosum produced five metabolites, including three new compounds, pseudolaric acid I (2), pseudolaric acid B 18-oyl-alanine (4) and pseudolaric acid B 18-oyl-serine (6), together with two known compounds, pseudolaric acid F (3) and pseudolaric acid B 18-oyl-glycine (5). The structures were characterized by NMR and MS spectroscopy. The major biotransformation reaction was conjugation with amino acids. None of the metabolites showed inhibitory effects on the growth of Candida albicans. The results suggested that biotransformation might be a detoxification process for fungi to resist antifungal drugs.