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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.

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Related in: MedlinePlus

Effects of small-molecule elicitors on the wentilactones production. WA (■); WB (□). Elicitors: MeOH (methanol, 3%), EtOH (ethanol, 3%), DMSO (dimethylsulfoxide, 3%), 5-AC (5-azacytidine, 100 μM), SBHA (suberohydroxamic acid, 100 μM), MeJA (methyl jasmonate, 100 μM).
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marinedrugs-13-07040-f006: Effects of small-molecule elicitors on the wentilactones production. WA (■); WB (□). Elicitors: MeOH (methanol, 3%), EtOH (ethanol, 3%), DMSO (dimethylsulfoxide, 3%), 5-AC (5-azacytidine, 100 μM), SBHA (suberohydroxamic acid, 100 μM), MeJA (methyl jasmonate, 100 μM).

Mentions: Three organic solvents (methanol, ethanol, and DMSO) with 3% final concentration, DNA methyltransferase inhibitor 5-AC, histone deacetylase inhibitor SBHA, and plant hormone MeJA with 100 μM were added to the culture for their effects on wentilactone production. With the treatment of 3% methanol on day 15, the production of WA and WB increased to 18.5 and 9.3 mg/L, respectively (Figure 6). Wentilactone yield increased slightly by feeding with MeJA, while a slight decrease was observed with the addition of ethanol, DMSO, 5-AC, and SBHA. Chemical elicitation using small molecules is proving to be an effective way for enhanced production and activation of silent microbial secondary metabolites. Some organic solvents may induce stress response and increases the synthesis of antibiotics [29]. The DNA methyltransferase and histone deacetylase inhibitors might activate unknown cryptic metabolic pathways by epigenetic modifications [16]. Rational design of the optimal time and concentration for the induction of secondary metabolites by addition of small-molecule elicitors still needs detailed investigation. The specific elicitation mechanisms and signal transduction pathways are very interesting for further study.


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)

Effects of small-molecule elicitors on the wentilactones production. WA (■); WB (□). Elicitors: MeOH (methanol, 3%), EtOH (ethanol, 3%), DMSO (dimethylsulfoxide, 3%), 5-AC (5-azacytidine, 100 μM), SBHA (suberohydroxamic acid, 100 μM), MeJA (methyl jasmonate, 100 μM).
© Copyright Policy
Related In: Results  -  Collection

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

marinedrugs-13-07040-f006: Effects of small-molecule elicitors on the wentilactones production. WA (■); WB (□). Elicitors: MeOH (methanol, 3%), EtOH (ethanol, 3%), DMSO (dimethylsulfoxide, 3%), 5-AC (5-azacytidine, 100 μM), SBHA (suberohydroxamic acid, 100 μM), MeJA (methyl jasmonate, 100 μM).
Mentions: Three organic solvents (methanol, ethanol, and DMSO) with 3% final concentration, DNA methyltransferase inhibitor 5-AC, histone deacetylase inhibitor SBHA, and plant hormone MeJA with 100 μM were added to the culture for their effects on wentilactone production. With the treatment of 3% methanol on day 15, the production of WA and WB increased to 18.5 and 9.3 mg/L, respectively (Figure 6). Wentilactone yield increased slightly by feeding with MeJA, while a slight decrease was observed with the addition of ethanol, DMSO, 5-AC, and SBHA. Chemical elicitation using small molecules is proving to be an effective way for enhanced production and activation of silent microbial secondary metabolites. Some organic solvents may induce stress response and increases the synthesis of antibiotics [29]. The DNA methyltransferase and histone deacetylase inhibitors might activate unknown cryptic metabolic pathways by epigenetic modifications [16]. Rational design of the optimal time and concentration for the induction of secondary metabolites by addition of small-molecule elicitors still needs detailed investigation. The specific elicitation mechanisms and signal transduction pathways are very interesting for further study.

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