Journal
JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
Volume 36, Issue 3, Pages 381-389Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s10295-008-0507-6
Keywords
Aspergillus glaucus; Aspergiolide A; Statistical methodologies; Medium optimization; Carbon-nitrogen ratio
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Funding
- National High Technology Research and Development Program of China [2006AA09Z429]
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Statistical methodologies were employed to optimize submerged culture medium for the production of a novel antineoplastic compound aspergiolide A by a marine-derived fungus Aspergillus glaucus HB1-19 for the first time. Orthogonal design was preformed to determine the initial composition. Then Plackett-Burman design was applied to evaluate the influence of related nutrients, and yeast extract paste, soybean powder and sodium glutamate were confirmed as critical factors in the medium. Response surface methodology (RSM) was finally taken as an effective approach to optimize the combination of the obtained three significant factors. The predicted maximal aspergiolide A production of 62.4 mg/L appeared at the region where the concentrations of sodium glutamate, soybean powder, and yeast extract paste were 2, 1, and 1.07 g/L, respectively. Under the proposed optimized conditions, the experimental aspergiolide A production reached 71.2 mg/L. The correlation between predicted value and measured value of these experiments proved the validity of the response model. After optimization, aspergiolide A production increased 4.22 times compared to that of the original medium. Elemental analysis was finally taken into consideration, and carbon-nitrogen ratio in the medium increased from 20.1:1 to 86.6:1. This great difference was inferred as the most important reason for production enhancement by metabolic pathway analysis.
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