Limits...
Characterization of a Newly Isolated Marine Fungus Aspergillus dimorphicus for Optimized Production of the Anti-Tumor Agent Wentilactones.

Xu R, Xu GM, Li XM, Li CS, Wang BG - Mar Drugs (2015)

Bottom Line: The result was further verified by fermentation scale-up for wentilactone production.Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production.The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Nanhai Road 7, Qingdao 266071, China. xrxurui@yeah.net.

ABSTRACT
The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields. In order to improve wentilactone production, culture conditions were optimized using the response surface methodology. Under the optimal static fermentation conditions, the experimental values were closely consistent with the prediction model. The yields of wentilactone A and B were increased about 11-fold to 13.4 and 6.5 mg/L, respectively. The result was further verified by fermentation scale-up for wentilactone production. Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production. To our knowledge, this is first report of optimized production of tetranorlabdane diterpenoids by a deep-sea derived marine fungus. The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.

Show MeSH

Related in: MedlinePlus

Response surface plots for maximal production of wentilactones. WA: (A) pH and salinity; (B) salinity and culture time; WB: (C) salinity and culture time. The Box-Behnken design of three factors and three levels and experimental results are shown in Table 1.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4663565&req=5

marinedrugs-13-07040-f005: Response surface plots for maximal production of wentilactones. WA: (A) pH and salinity; (B) salinity and culture time; WB: (C) salinity and culture time. The Box-Behnken design of three factors and three levels and experimental results are shown in Table 1.

Mentions: The regression equation describing the relationship between the WA production and the test variables in coded units is:Ya = 12.75 + 1.64X1 + 1.77X2 + 1.75X3 + 1.04X1X2 + 0.44X2X3 − 1.50X12 − 3.56X22 − 2.54X32(1)where Ya is the predicted response of WA production; X1, X2, and X3 are the coded values of pH, salinity, and culture time, respectively. The AVONA analysis results of WA were shown in Table 2. The model F-value of 67.53 and p-value of 0.0012 indicate that model terms are significant. The lack of fit, with the F-value of 1.02, is insignificant. The coefficient of determination (R2) was calculated as 0.9890 for the WA production, indicating that the statistical model can explain 98.90% of variability in the response (Table 2). Adequate precision measures the signal-to-noise ratio. An adequate precision of 22.764 for the WA production was recorded. The predicted R2 value is in reasonable agreement with the value of adjusted R2. This indicates good agreement between the experimental and predicted values for WA production. Thus it could be applied to predict the theoretical WA production. The results of the regression parameter estimate indicated that linear and square terms of pH (X1), salinity (X2), and culture time (X3) values, as well as the interaction term of pH (X1) and salinity (X2) were highly significant (p< 0.05). The relation between factors and WA production was indicated by the 3D surface (Figure 5A,B).


Characterization of a Newly Isolated Marine Fungus Aspergillus dimorphicus for Optimized Production of the Anti-Tumor Agent Wentilactones.

Xu R, Xu GM, Li XM, Li CS, Wang BG - Mar Drugs (2015)

Response surface plots for maximal production of wentilactones. WA: (A) pH and salinity; (B) salinity and culture time; WB: (C) salinity and culture time. The Box-Behnken design of three factors and three levels and experimental results are shown in Table 1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663565&req=5

marinedrugs-13-07040-f005: Response surface plots for maximal production of wentilactones. WA: (A) pH and salinity; (B) salinity and culture time; WB: (C) salinity and culture time. The Box-Behnken design of three factors and three levels and experimental results are shown in Table 1.
Mentions: The regression equation describing the relationship between the WA production and the test variables in coded units is:Ya = 12.75 + 1.64X1 + 1.77X2 + 1.75X3 + 1.04X1X2 + 0.44X2X3 − 1.50X12 − 3.56X22 − 2.54X32(1)where Ya is the predicted response of WA production; X1, X2, and X3 are the coded values of pH, salinity, and culture time, respectively. The AVONA analysis results of WA were shown in Table 2. The model F-value of 67.53 and p-value of 0.0012 indicate that model terms are significant. The lack of fit, with the F-value of 1.02, is insignificant. The coefficient of determination (R2) was calculated as 0.9890 for the WA production, indicating that the statistical model can explain 98.90% of variability in the response (Table 2). Adequate precision measures the signal-to-noise ratio. An adequate precision of 22.764 for the WA production was recorded. The predicted R2 value is in reasonable agreement with the value of adjusted R2. This indicates good agreement between the experimental and predicted values for WA production. Thus it could be applied to predict the theoretical WA production. The results of the regression parameter estimate indicated that linear and square terms of pH (X1), salinity (X2), and culture time (X3) values, as well as the interaction term of pH (X1) and salinity (X2) were highly significant (p< 0.05). The relation between factors and WA production was indicated by the 3D surface (Figure 5A,B).

Bottom Line: The result was further verified by fermentation scale-up for wentilactone production.Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production.The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Nanhai Road 7, Qingdao 266071, China. xrxurui@yeah.net.

ABSTRACT
The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields. In order to improve wentilactone production, culture conditions were optimized using the response surface methodology. Under the optimal static fermentation conditions, the experimental values were closely consistent with the prediction model. The yields of wentilactone A and B were increased about 11-fold to 13.4 and 6.5 mg/L, respectively. The result was further verified by fermentation scale-up for wentilactone production. Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production. To our knowledge, this is first report of optimized production of tetranorlabdane diterpenoids by a deep-sea derived marine fungus. The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.

Show MeSH
Related in: MedlinePlus