Mycophenolic acid production by drug-resistant and methionine or glutamic-acid requiring mutants of Penicillium brevicompactum.

Penicillium brevicompactum ATCC 16024 produced 1.7 g/1 of mycophenolic acid (MPA) in the culture medium. Various drug-resistant mutants, showing resistance to such as polyene antibiotics, chemotherapeutic agents, redox indicator and surfactants, were derived from the fungus. Most of the mutants produced 2.0 ~2.5 g/1 of MPA. A clofibrate and dodecyltrimethylammonium chloride double resistant mutant, No. 4–23–11, produced 4.7 g/1 of MPA. A monofluoroacetic acid resistant strain, No. 5–1, derived from No. 4–23–11 produced 5.3 g/1 of MPA.A methionine auxotroph, M-l, derived from ATCC 16024, produced 4.0 g/1 of MPA. A glutamate auxotroph, G-42, derived from strain No. 4–23–11 produced 5.8 g/1 of MPA. G-42 grew on l-aspartate instead of l-glutamate, and showed one-third the pyruvate carboxylase activity of the parent. Another glutamate auxotroph, G-78, did not produce MPA but accumulated 1.5 g/1 of acetate in the culture medium, and showed one-fifth the citrate synthase activity of the parent strain.