Mutants of a lovastatin-hyperproducingAspergillus terreus deficient in the production of sulochrin |
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Authors: | V. A. Vinci T. D. Hoerner A. D. Coffman T. G. Schimmel R. L. Dabora A. C. Kirpekar C. L. Ruby R. W. Stieber |
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Affiliation: | (1) MCMD, Merck & Co., P.O. Box 7, 22827 Elkton, VA, USA;(2) MSDRL, Merck & Co, Rahway, New Jersey, USA |
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Abstract: | Summary A lovastatin-hyperproducing culture ofAspergillus terreus was shown to produce several co-metabolites extracted from whole broth. The predominant co-metabolite was the benzophenone, sulochrin, reported to arise from a polyketide biosynthetic pathway. This compound was targeted for elimination by classical mutagenesis and screening. A surface culture method employing microtiter, plates was used to ferment mutants for the primary screen. Qualitative determinations of lovastatin and sulochrin production were achieved by high-performance thin-layer chromatography. A mutant, strain AH6, which produced lovastatin titers equivalent to the parent culture and no detectable sulochrin was isolated. In addition, a lovastatin-hyperproducing mutant designated CB4 was capable of producing 16% more lovastatin and 30% less sulochrin than the parent culture in shake flask fermentations. In a pilot-scale 250-gallon fermentation, strain CB4 gave a 20% increase in lovastatin titer while producing 83% less sulochrin than the parent culture. |
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Keywords: | Microtiter fermentation Lovastatin Polyketide Strain improvement Screening |
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