Abstract
In the context of research for new cytotoxic compounds, obtaining bioactive molecules from renewable sources remain a big challenge. Microorganisms and more specifically Actinobacteria from original sources are well known for their biotechnological potential and are hotspots for the discovery of new bioactive compounds. The strain DP94 studied here had shown an interesting cytotoxic activity of its culture broth (HaCaT: IC50 = 8.0 ± 1.5 μg/mL; B16: IC50 = 4.6 ± 1.8 μg/mL), which could not been explained by the compounds isolated in a previous work. The increase of the cytotoxic activity of extracts was investigated, based on a Taguchi L9 orthogonal array design, after DP94 culture in TY medium using two different vessels (bioreactor or Erlenmeyer flasks). Various culture parameters such as temperature, pH and inoculum ratio (%) were studied. For experiments conducted in a bioreactor, stirring speed was included as an additional parameter. Significant differences in the cytotoxic activities of different extracts on B16 melanoma cancer cell lines, highlighted the influence of culture temperature on the production of cytotoxic compound(s) using a bioreactor. A culture in Erlenmeyer flasks was also performed and afforded an increase of the production of the active compounds. The best conditions for the highest cytotoxicity (IC50 on B16: 6 ± 0.5 μg/mL) and the highest yield (202.0 mg/L) were identified as: pH 6, temperature 37°C and 5% inoculum.
Highlights
Some antibiotics such as actinomycin, streptothricin and streptomycin have been discovered since the forties [1]
Actinobacteria produce a wide variety of secondary metabolites with interesting biological activities such as insecticidal, antifungal, antiviral, and cytotoxic activities
The results detailed showed that the production of cytotoxic compounds by this Nocardia sp. could be modulated by culture conditions according to the One Strain Many Compounds (OSMAC) (One Strain/Many Compounds) approach previously described [23]
Summary
Some antibiotics such as actinomycin, streptothricin and streptomycin have been discovered since the forties [1].
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