The Experts below are selected from a list of 6657 Experts worldwide ranked by ideXlab platform
Yong Yang - One of the best experts on this subject based on the ideXlab platform.
-
enhanced single step Bioproduction of the simvastatin precursor monacolin j in an industrial strain of aspergillus terreus by employing the evolved lovastatin hydrolase
Biotechnology Journal, 2018Co-Authors: Bo Liang, Xuenian Huang, Yajing Liang, Yong Yang, Yun Teng, Linghui ZhengAbstract:Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 °C increased T5010 over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step Bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete Bioproduction of simvastatin at industrial scale.
-
single step production of the simvastatin precursor monacolin j by engineering of an industrial strain of aspergillus terreus
Metabolic Engineering, 2017Co-Authors: Xuenian Huang, Yajing Liang, Yong YangAbstract:Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct Bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete Bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.
Xuenian Huang - One of the best experts on this subject based on the ideXlab platform.
-
enhanced single step Bioproduction of the simvastatin precursor monacolin j in an industrial strain of aspergillus terreus by employing the evolved lovastatin hydrolase
Biotechnology Journal, 2018Co-Authors: Bo Liang, Xuenian Huang, Yajing Liang, Yong Yang, Yun Teng, Linghui ZhengAbstract:Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 °C increased T5010 over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step Bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete Bioproduction of simvastatin at industrial scale.
-
single step production of the simvastatin precursor monacolin j by engineering of an industrial strain of aspergillus terreus
Metabolic Engineering, 2017Co-Authors: Xuenian Huang, Yajing Liang, Yong YangAbstract:Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct Bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete Bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.
Mausam P. Verma - One of the best experts on this subject based on the ideXlab platform.
-
Bioproduction and extraction optimization of citric acid from Aspergillus niger by rotating drum type solid-state bioreactor.
Industrial Crops and Products, 2013Co-Authors: Gurpreet Singh Dhillon, Satinder Kaur Brar, Surinder Kaur, Mausam P. VermaAbstract:Abstract Solid-state citric acid fermentation was conducted in a 12-L rotating drum type bioreactor. The effect of inducers, ethanol and methanol were studied on citric acid Bioproduction by Aspergillus niger NRRL 567 cultivated on apple pomace as a solid-substrate. Optimum conditions achieved for higher citric acid Bioproduction (220.6 ± 13.9 g/kg dry solids, DS) were 3% (v/v) methanol, intermittent agitation of 1 h after every 12 h at 2 rpm and 1 vvm of aeration rate and 120 h incubation time. The response surface optimization proved effective for higher citric acid extraction from fermented solid-substrate. Higher citric acid extraction of 294.19 g/kg DS was achieved at optimum conditions: extraction time of 20 min, agitation rate of 200 rpm and extractant volume of 15 ml by response surface methodology.
-
Potential of apple pomace as a solid substrate for fungal cellulase and hemicellulase Bioproduction through solid-state fermentation
Industrial Crops and Products, 2012Co-Authors: Gurpreet Singh Dhillon, Satinder Kaur Brar, Surinder Kaur, Mausam P. VermaAbstract:The effect of different inducers on the cellulase and hemicellulase Bioproduction by Aspergillus niger NRRL-567 using apple pomace as a substrate was investigated. Rapid production of different cellulase enzymes namely, FPase (filter paper cellulase), CMCase (carboxymethyl cellulase), BGL (β-glucosidase), and xylanase were observed with peak activity reaching between 48 and 72 h of fermentation period. The higher FPase and BGL activities of 133.68 ± 5.44 IU/gram dry substrate (gds) and 60.09 ± 3.43 IU/gds, respectively were observed while using CuSO4 and veratryl alcohol after 48 h of incubation time. The higher CMCase activity of 172.31 ± 14.21 IU/gds was obtained with lactose after 48 h of incubation period. Similarly, higher xylanase activity of 1412.58 ± 27.9 IU/gds was observed with veratryl alcohol after 72 h of fermentation time. This study sheds light on the rapid Bioproduction of fungal cellulase and hemicellulase using low cost waste, apple pomace as substrate when supplemented with different inducers.
-
Biotechnological potential of industrial wastes for economical citric acid Bioproduction by Aspergillus niger through submerged fermentation
International Journal of Food Science & Technology, 2011Co-Authors: Gurpreet Singh Dhillon, Satinder Kaur Brar, Mausam P. VermaAbstract:Summary Submerged citric acid (CA) Bioproduction was carried out by Aspergillus niger NRRL-567 using various industrial wastes, such as brewery spent liquid (BSL), lactoserum and starch industry water sludge. CA Bioproduction was carried out by varying the temperature (25–35 °C), pH (3–5), addition of inducers, incubation time and supplementation with different proportions of apple pomace ultrafiltration sludge (APS). The results indicated that under the best conditions with 3% (v/v) methanol, the optimal concentration of 11.34 g L−1 CA was recorded using BSL at pH 3.5 and temperature 30 °C after 120-h incubation period. Supplementation of methanol resulted in an increase of 56% CA production. Meanwhile, under similar conditions, higher concentration of 18.34 g L−1 CA was reported with the supplementation of BSL with 40% (v/v) APS having suspended solids concentration of 30 g L−1. The present study demonstrated the potential of BSL supplemented with APS as an alternative cheap substrate for CA fermentation.
Yajing Liang - One of the best experts on this subject based on the ideXlab platform.
-
enhanced single step Bioproduction of the simvastatin precursor monacolin j in an industrial strain of aspergillus terreus by employing the evolved lovastatin hydrolase
Biotechnology Journal, 2018Co-Authors: Bo Liang, Xuenian Huang, Yajing Liang, Yong Yang, Yun Teng, Linghui ZhengAbstract:Biosynthesis of simvastatin, the active pharmaceutical ingredient of cholesterol-lowering drug Zocor, has drawn increasing global attention in recent years. Although single-step in vivo production of monacolin J, the intermediate biosynthetic precursor of simvastatin, has been realized by utilizing lovastatin hydrolase (PcEST) in our previous study, about 5% of residual lovastatin is still a problem for industrial production and quality control. In order to improve conversion efficiency and reduce lovastatin residues, modification of PcEST is carried out through directed evolution and a novel two-step high-throughput screening method. The mutant Q140L shows 18-fold improved whole-cell activity as compared to the wild-type, and one fold enhanced catalytic efficiency and 3 °C increased T5010 over the wild-type are observed by characterizing the purified protein. Finally, the engineered A. terreus strain overexpressing Q140L mutant exhibited the increased conversion efficiency and the reduced lovastatin residues by comparing with A. terreus strain overexpressing the wild-type PcEST, where almost 100% of the produced lovastatin is hydrolyzed to monacolin J. Therefore, this improved microbial cell factory can realize single-step Bioproduction of monacolin J in a more efficient way, providing an attractive and eco-friendly substitute over the existing chemical synthetic routes of monacolin J and promoting complete Bioproduction of simvastatin at industrial scale.
-
single step production of the simvastatin precursor monacolin j by engineering of an industrial strain of aspergillus terreus
Metabolic Engineering, 2017Co-Authors: Xuenian Huang, Yajing Liang, Yong YangAbstract:Monacolin J is a key precursor for the synthesis of simvastatin (Zocor), an important drug for treating hypercholesterolemia. Industrially, monacolin J is manufactured through alkaline hydrolysis of lovastatin, a fungal polyketide produced by Aspergillus terreus. Multistep chemical processes for the conversion of lovastatin to simvastatin are laborious, cost expensive and environmentally unfriendly. A biocatalysis process for monacolin J conversion to simvastatin has been developed. However, direct Bioproduction of monacolin J has not yet been achieved. Here, we identified a lovastatin hydrolase from Penicillium chrysogenum, which displays a 232-fold higher catalytic efficiency for the in vitro hydrolysis of lovastatin compared to a previously patented hydrolase, but no activity for simvastatin. Furthermore, we showed that an industrial A. terreus strain heterologously expressing this lovastatin hydrolase can produce monacolin J through single-step fermentation with high efficiency, approximately 95% of the biosynthesized lovastatin was hydrolyzed to monacolin J. Our results demonstrate a simple and green technical route for the production of monacolin J, which makes complete Bioproduction of the cholesterol-lowering drug simvastatin feasible and promising.
Satinder Kaur Brar - One of the best experts on this subject based on the ideXlab platform.
-
Bioproduction of fumaric acid: an insight into microbial strain improvement strategies.
Critical reviews in biotechnology, 2019Co-Authors: Joseph Sebastian, Krishnamoorthy Hegde, Pratik Kumar, Tarek Rouissi, Satinder Kaur BrarAbstract:Fumaric acid (FA), a metabolic intermediate, has been identified as an important carbohydrate derived platform chemical. Currently, it is commercially sourced from petrochemicals by chemical conversion. The shift to biochemical synthesis has become essential for sustainable development and for the transition to a biobased economy from a petroleum-based economy. The main limitation is that the concentrations of FA achieved during Bioproduction are lower than that from a chemical process. Moreover, the high cost associated with Bioproduction necessitates a higher yield to improve the feasibility of the process. To this effect, genetic modification of microorganism can be considered as an important tool to improve FA yield. This review discusses various genetic modifications strategies that have been studied in order to improve FA production. These strategies include the development of recombinant strains of Rhizopus oryzae, Escherichia coli, Saccharomyces cerevisiae, and Torulopsis glabrata as well as their mutants. The transformed strains were able to accumulate fumaric acid at a higher concentration than the corresponding wild strains but the fumaric acid titers obtained were lower than that reported with native fumaric acid producing R. oryzae strains. Moreover, one plausible adoption of gene editing tools, such as Agrobacterium-mediated transformation (AMT), CRISPR CAS-9 and RNA interference (RNAi) mediated knockout and silencing, have been proposed in order to improve fumaric acid yield. Additionally, the introduction of the glyoxylate pathway in R. oryzae to improve fumaric acid yield as well as the biosynthesis of fumarate esters have been proposed to improve the economic feasibility of the bioprocess. The adoption of some of these genetic engineering strategies may be essential to enable the development of a feasible Bioproduction process.
-
Bioproduction and extraction optimization of citric acid from Aspergillus niger by rotating drum type solid-state bioreactor.
Industrial Crops and Products, 2013Co-Authors: Gurpreet Singh Dhillon, Satinder Kaur Brar, Surinder Kaur, Mausam P. VermaAbstract:Abstract Solid-state citric acid fermentation was conducted in a 12-L rotating drum type bioreactor. The effect of inducers, ethanol and methanol were studied on citric acid Bioproduction by Aspergillus niger NRRL 567 cultivated on apple pomace as a solid-substrate. Optimum conditions achieved for higher citric acid Bioproduction (220.6 ± 13.9 g/kg dry solids, DS) were 3% (v/v) methanol, intermittent agitation of 1 h after every 12 h at 2 rpm and 1 vvm of aeration rate and 120 h incubation time. The response surface optimization proved effective for higher citric acid extraction from fermented solid-substrate. Higher citric acid extraction of 294.19 g/kg DS was achieved at optimum conditions: extraction time of 20 min, agitation rate of 200 rpm and extractant volume of 15 ml by response surface methodology.
-
Potential of apple pomace as a solid substrate for fungal cellulase and hemicellulase Bioproduction through solid-state fermentation
Industrial Crops and Products, 2012Co-Authors: Gurpreet Singh Dhillon, Satinder Kaur Brar, Surinder Kaur, Mausam P. VermaAbstract:The effect of different inducers on the cellulase and hemicellulase Bioproduction by Aspergillus niger NRRL-567 using apple pomace as a substrate was investigated. Rapid production of different cellulase enzymes namely, FPase (filter paper cellulase), CMCase (carboxymethyl cellulase), BGL (β-glucosidase), and xylanase were observed with peak activity reaching between 48 and 72 h of fermentation period. The higher FPase and BGL activities of 133.68 ± 5.44 IU/gram dry substrate (gds) and 60.09 ± 3.43 IU/gds, respectively were observed while using CuSO4 and veratryl alcohol after 48 h of incubation time. The higher CMCase activity of 172.31 ± 14.21 IU/gds was obtained with lactose after 48 h of incubation period. Similarly, higher xylanase activity of 1412.58 ± 27.9 IU/gds was observed with veratryl alcohol after 72 h of fermentation time. This study sheds light on the rapid Bioproduction of fungal cellulase and hemicellulase using low cost waste, apple pomace as substrate when supplemented with different inducers.
-
Biotechnological potential of industrial wastes for economical citric acid Bioproduction by Aspergillus niger through submerged fermentation
International Journal of Food Science & Technology, 2011Co-Authors: Gurpreet Singh Dhillon, Satinder Kaur Brar, Mausam P. VermaAbstract:Summary Submerged citric acid (CA) Bioproduction was carried out by Aspergillus niger NRRL-567 using various industrial wastes, such as brewery spent liquid (BSL), lactoserum and starch industry water sludge. CA Bioproduction was carried out by varying the temperature (25–35 °C), pH (3–5), addition of inducers, incubation time and supplementation with different proportions of apple pomace ultrafiltration sludge (APS). The results indicated that under the best conditions with 3% (v/v) methanol, the optimal concentration of 11.34 g L−1 CA was recorded using BSL at pH 3.5 and temperature 30 °C after 120-h incubation period. Supplementation of methanol resulted in an increase of 56% CA production. Meanwhile, under similar conditions, higher concentration of 18.34 g L−1 CA was reported with the supplementation of BSL with 40% (v/v) APS having suspended solids concentration of 30 g L−1. The present study demonstrated the potential of BSL supplemented with APS as an alternative cheap substrate for CA fermentation.