Enhanced production of a novel cytotoxic chromone oxalicumone A by marine-derived mutant Penicillium oxalicum SCSIO 24–2

Abstract

Many marine natural products hold great potential for the development of new and much needed drugs. However, the production of active metabolites by marine-derived microorganisms is usually very low, and large-scale culture has to be involved to meet the need of chemical structural modification and deep pharmacy study. In order to enhance the production of a novel cytotoxic sulfur-containing chromone oxalicumone A (OA), germinating spores of a marine-derived wild strain Penicillium oxalicum SCSGAF 0023 were mutated by microwave and ultraviolet light irradiation, which led to the obtainment of a mutant P. oxalicum SCSIO 24-2 that could produce fivefold increase in OA production (3.42±0.21 mg/l) as compared to the wild strain. This is the first report that germinating spores are applied in marine-derived Penicillium sp. mutating to enhance the production of OA. Further, Plackett-Burman design and central composite design were adopted to optimize the basic medium components for increasing OA production by the mutant SCSIO 24-2 in shake flasks. The results indicated that three medium components including mannitol, maltose, and L -cysteine had significant effects on OA production, and their concentrations were optimized as 36, 27.9, and 0.99 g/l, respectively. In the optimized medium, the OA production (18.31±0.27 mg/l) by mutant SCSIO 24-2 was 4.4-fold higher than that in the basic medium. These results of this work promise to improve the present production of OA and may be adopted to enhance other objective products' production by marine-derived fungi.

Production of Calcaride A by Calcarisporium sp. in Shaken Flasks and Stirred Bioreactors

“…Zhou et al [ 6 ] and Tamminen et al [ 7 ] found that conditions which promoted good biomass production promoted the production of 1403C (an anthracycline analogue) and scopularide A, respectively. The carbon–nitrogen ratio is important in the regulation of both fatty acid and polyketide synthesis and was optimized to enhance production of oxalicumone A [ 22 ]. Both carbon and nitrogen sources may be important [ 8 , 22 ].…”

“…The carbon–nitrogen ratio is important in the regulation of both fatty acid and polyketide synthesis and was optimized to enhance production of oxalicumone A [ 22 ]. Both carbon and nitrogen sources may be important [ 8 , 22 ].…”

Hepatocellular toxicity of oxalicumone A via oxidative stress injury and mitochondrial dysfunction in healthy human liver cells

“…POA was isolated from a culture broth of the South China Sea fungus Penicillium oxalicum SCSGAF 0023 ( 8 ). Although POA has previously been indicated to induce cytotoxicity in human carcinoma ( 12 ), to the best of our knowledge, there have not been previous studies on the cytotoxicity of POA on L-02 cells human normal liver cells, which has been a major limitation in the clinical application of POA. The present study investigated POA-induced cytotoxicity and its toxic mechanisms in L-02 cells.…”

Total Synthesis of (±)‐Oxalicumone C and Chiral Resolution and Elucidation of Its Absolute Configuration

“…Coniochaetones E ( 3 ) and F ( 4 ) are derived from the soil fungus Penicillium citrinum PSU‐RSPG95 and are currently under evaluation for their cytotoxic behavior 13. Isolation and structure elucidation of dihydrothiophene‐annulated chromones, for example, oxalicumone A ( 2 ) was recently reported by Qi et al, who also found oxalicumone C ( 5 ) in the marine‐derived fungus Penicillium oxalicum 8,14…”