Mycophenolic Acid Production by Drug-resistant and Methionine or Glutamic-Acid Requiring Mutants of Penicillium brevicompactum

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Penicillium brevicompactum ATCC 16024 produced 1.7g/l 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/l of MPA. A clofibrate and dodecyltrimethylammonium chloride double resistant mutant, No. 4-23-11, produced 4.7 g/l of MPA. A monofluoroacetic acid resistant strain, No. 5-1, derived from No. 4-23-11 produced 5.3 g/l of MPA. A methionine auxotroph, M-1, derived from ATCC 16024, produced 4.0 g/l of MPA. A glutamate auxotroph, G-42, derived from strain No. 4-23-11 produced 5.8 g/l 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/l of acetate in the culture medium, and showed one-fifth the citrate synthase activity of the parent strain.
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