Actinomycetes have been prolific sources of novel secondary metabolites with a range of biological activities that may ultimately find application as therapeutic compounds. Hence several drug discovery companies are e...Actinomycetes have been prolific sources of novel secondary metabolites with a range of biological activities that may ultimately find application as therapeutic compounds. Hence several drug discovery companies are engaged in isolation of novel bioactive metabolites from these microbial sources. Antibiotics form the major class of such bioactive metabolites and have been widely used for treating infectious diseases. One of the most critical problems in clinical practice is the increase of prevalence of drug resistant strains, especially azole resistance among fungi. Due to this, there is a constant need for development of new antifungal antibiotics having novel scaffolds and/or mechanism of action. In our in-house screening program in the quest of novel and superior antifungal compounds, an actinomycetes strain PM0525875 was isolated from a marine invertebrate. The extracts of this microbe showed potent in-vitro antifungal activity against drug resistant fungal strains. The antifungal active peak from the extract obtained by shake flask fermentation was identified by chromatographic and other analytical techniques during bioactivity guided isolation. Later the fermentation conditions were optimized in 30 L fermentor for the production of sufficient amount antifungal compound for complete structural characterization. Consequently the fermented broth extract was subjected to bioactivity-guided fractionation, to isolate the active principle using different preparative chromatographic techniques followed by its characterization. The active principle was characterized to be Caerulomycin A. Minimum inhibitory concentration (MIC) of the compound was found in the range of 0.39 - 1.56 μg/ml against pathogenic fungal test strains. The phylogenetic analysis of producer strain using 16S rRNA sequence showed closest match with Actinoalloateichus cyanogriseus. Herewith we report the isolation of Caerulomycin A from marine invertebrate-associated Actinoalloteichus sp. using optimized medium and fermentation conditions.展开更多
Coenzyme Q10 (CoQ10), an important antioxidant molecule playing a major role in electron transport chain, has been commercially produced by fermentation process for the use in oral nutraceutical formulations. Construc...Coenzyme Q10 (CoQ10), an important antioxidant molecule playing a major role in electron transport chain, has been commercially produced by fermentation process for the use in oral nutraceutical formulations. Constructing the high-yielding CoQ10 producing strains is a pre-requisite for cost-effective production. A superior mutant strain P-87 generated from Paracoccus denitrificans ATCC 19367, which showed 1.25-fold improvement in specific CoQ10 content higher than the wild type strain at shake flask level, was selected to carry out the studies on CoQ10 yield improvement through fermenter process optimization. In the course of study, initially the cane-molasses-based medium and fed-batch fermentation strategy using pHBA in combination with sucrose were standardized in shake flask using wild type strain. This strategy was subsequently translated at 2 L laboratory fermenter while optimizing the fermentation process parameters using improved mutant strain P-87. Under optimized fermentation condition, mutant strain P-87 produced 49.85 mg/L of CoQ10 having specific content of 1.63 mg/g of DCW, which was 1.36 folds higher than the specific CoQ10 content of wild-type strain under similar optimized condition. The temperature and DO were found to be critical parameters for CoQ10 production by mutant strain P-87. The optimum temperature was found to be 32°C and the optimum DO concentration to be maintained throughout the fermentation cycle was found to be 30% of air saturation. Overall, a new cost-effective process has been established for the production of CoQ10 using the cheaper substrate “cane molasses” and higher CoQ10 producing mutant strain P-87.展开更多
文摘Actinomycetes have been prolific sources of novel secondary metabolites with a range of biological activities that may ultimately find application as therapeutic compounds. Hence several drug discovery companies are engaged in isolation of novel bioactive metabolites from these microbial sources. Antibiotics form the major class of such bioactive metabolites and have been widely used for treating infectious diseases. One of the most critical problems in clinical practice is the increase of prevalence of drug resistant strains, especially azole resistance among fungi. Due to this, there is a constant need for development of new antifungal antibiotics having novel scaffolds and/or mechanism of action. In our in-house screening program in the quest of novel and superior antifungal compounds, an actinomycetes strain PM0525875 was isolated from a marine invertebrate. The extracts of this microbe showed potent in-vitro antifungal activity against drug resistant fungal strains. The antifungal active peak from the extract obtained by shake flask fermentation was identified by chromatographic and other analytical techniques during bioactivity guided isolation. Later the fermentation conditions were optimized in 30 L fermentor for the production of sufficient amount antifungal compound for complete structural characterization. Consequently the fermented broth extract was subjected to bioactivity-guided fractionation, to isolate the active principle using different preparative chromatographic techniques followed by its characterization. The active principle was characterized to be Caerulomycin A. Minimum inhibitory concentration (MIC) of the compound was found in the range of 0.39 - 1.56 μg/ml against pathogenic fungal test strains. The phylogenetic analysis of producer strain using 16S rRNA sequence showed closest match with Actinoalloateichus cyanogriseus. Herewith we report the isolation of Caerulomycin A from marine invertebrate-associated Actinoalloteichus sp. using optimized medium and fermentation conditions.
文摘Coenzyme Q10 (CoQ10), an important antioxidant molecule playing a major role in electron transport chain, has been commercially produced by fermentation process for the use in oral nutraceutical formulations. Constructing the high-yielding CoQ10 producing strains is a pre-requisite for cost-effective production. A superior mutant strain P-87 generated from Paracoccus denitrificans ATCC 19367, which showed 1.25-fold improvement in specific CoQ10 content higher than the wild type strain at shake flask level, was selected to carry out the studies on CoQ10 yield improvement through fermenter process optimization. In the course of study, initially the cane-molasses-based medium and fed-batch fermentation strategy using pHBA in combination with sucrose were standardized in shake flask using wild type strain. This strategy was subsequently translated at 2 L laboratory fermenter while optimizing the fermentation process parameters using improved mutant strain P-87. Under optimized fermentation condition, mutant strain P-87 produced 49.85 mg/L of CoQ10 having specific content of 1.63 mg/g of DCW, which was 1.36 folds higher than the specific CoQ10 content of wild-type strain under similar optimized condition. The temperature and DO were found to be critical parameters for CoQ10 production by mutant strain P-87. The optimum temperature was found to be 32°C and the optimum DO concentration to be maintained throughout the fermentation cycle was found to be 30% of air saturation. Overall, a new cost-effective process has been established for the production of CoQ10 using the cheaper substrate “cane molasses” and higher CoQ10 producing mutant strain P-87.
