Hypothemycin production and its derivatives diversifying of iAigialus parvus/iBCC 5311 influenced by cultural condition

摘要

Many metabolites produced by various microorganisms have proven their usefulness in the area concerning human health. However, most of their diverse natural compound biosyntheses are hardly discovered. These metabolites might have specific or novel functions and these diverse active compounds can be achieved by biosynthesis, semi-biosynthesis, or chemical synthesis. A strategy to exploit the biosynthesis potential of a fungal strain is to use various culture conditions and to evaluate the chemical profiles of the culture extracts. The value of this approach was demonstrated with the fungal strain Aigialus parvus BCC 5311, producer of hypothemycin, aigialospirol, and aigialomycin A-D. The optimization of hypothemycin production and its derivative diversity by Aigialus parvus BCC 5311 was carried out using qualitative (general factorial design) and quantitative analysis (two-level fractional factorial design). Qualitative analysis revealed that soluble starch and yeast extract were shown to be the best carbon and nitrogen source respectively for the production of hypothemycin, aigialospirol and aigialomycin A-D. Quantitative analysis showed that the initial pH of culture medium is the most important factor that affects the production of hypothemycin and its derivatives (aigialospirol and aigialomycin A-D) production. Optimal medium composition used in a 5 L bioreactor generated a specific growth rate of A. parvus BCC 5311 of 0.0295 h-1, biomass yield of 1.6 g×gstarch-1, hypothemycin yield of 13.6 mg×gbiomass-1, and hypothemycin production rate of 0.6 mg×L-1×day-1. The maximum concentration of 58.0 mg×L-1 of hypothemycin was obtained at 120 h of culturing. Furthermore, the Aigialomycin A-D and Aigialospirol obtained were diversified towards various cultural conditions used. The high amount of hypothemycin produced and the diversity of derivatives obtained from this study should be useful for future mass production.