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Lipase-Catalyzed Baeyer-Villiger Oxidation of Cellulose-Derived Levoglucosenone into (S)-γ-Hydroxymethyl-α,β-Butenolide: Optimization by Response Surface Methodology.

Teixeira AR, Flourat AL, Peru AA, Brunissen F, Allais F - Front Chem (2016)

Bottom Line: Response surface methodology (RSM), based on central composite face-centered (CCF) design, was employed to evaluate the factors effecting the enzyme-catalyzed reaction: pka of solid buffer (7.2-9.6), LGO concentration (0.5-1 M) and enzyme loading (55-285 PLU.mmol(-1)).Enzyme loading and pka of solid buffer were found to be important factors to the reaction efficiency (as measured by the conversion of LGO) while only the later had significant effects on the enzyme recyclability (as measured by the enzyme residual activity).A good agreement between experimental and predicted values was obtained and the model validity confirmed (p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Chaire Agro-Biotechnologies Industrielles, AgroParisTechReims, France; UMR GENIAL, AgroParisTech, Institut National de la Recherche Agronomique, Université Paris-SaclayMassy, France.

ABSTRACT
Cellulose-derived levoglucosenone (LGO) has been efficiently converted into pure (S)-γ-hydroxymethyl-α,β-butenolide (HBO), a chemical platform suited for the synthesis of drugs, flavors and antiviral agents. This process involves two-steps: a lipase-catalyzed Baeyer-Villiger oxidation of LGO followed by an acid hydrolysis of the reaction mixture to provide pure HBO. Response surface methodology (RSM), based on central composite face-centered (CCF) design, was employed to evaluate the factors effecting the enzyme-catalyzed reaction: pka of solid buffer (7.2-9.6), LGO concentration (0.5-1 M) and enzyme loading (55-285 PLU.mmol(-1)). Enzyme loading and pka of solid buffer were found to be important factors to the reaction efficiency (as measured by the conversion of LGO) while only the later had significant effects on the enzyme recyclability (as measured by the enzyme residual activity). LGO concentration influences both responses by its interaction with the enzyme loading and pka of solid buffer. The optimal conditions which allow to convert at least 80% of LGO in 2 h at 40°C and reuse the enzyme for a subsequent cycle were found to be: solid buffer pka = 7.5, [LGO] = 0.50 M and 113 PLU.mmol(-1) for the lipase. A good agreement between experimental and predicted values was obtained and the model validity confirmed (p < 0.05). Alternative optimal conditions were explored using Monte Carlo simulations for risk analysis, being estimated the experimental region where the LGO conversion higher than 80% is fulfilled at a specific risk of failure.

No MeSH data available.


Related in: MedlinePlus

Design space plot. Contours indicate the risk of failure (%) in the specifications fulfilling (LGO conversion > 80%, pkaHEPES = 7.5). Green color indicates the area where the risk of failure is lower (< 1%), while the red indicates a higher risk of failure (> 2%). Point A- optimum identified by a Nelder-Mead Simplex algorithm (194 PLU.mmol-1 and [LGO] = 0.50 M), Point B - optimum identified in an earlier publication (Flourat et al., 2014) (113 PLU.mmol-1 and [LGO] = 0.75 M); Point C - point with a zero risk level (227 PLU.mmol-1 and [LGO] = 0.75 M).
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Figure 6: Design space plot. Contours indicate the risk of failure (%) in the specifications fulfilling (LGO conversion > 80%, pkaHEPES = 7.5). Green color indicates the area where the risk of failure is lower (< 1%), while the red indicates a higher risk of failure (> 2%). Point A- optimum identified by a Nelder-Mead Simplex algorithm (194 PLU.mmol-1 and [LGO] = 0.50 M), Point B - optimum identified in an earlier publication (Flourat et al., 2014) (113 PLU.mmol-1 and [LGO] = 0.75 M); Point C - point with a zero risk level (227 PLU.mmol-1 and [LGO] = 0.75 M).

Mentions: Alternative optimal conditions can be explored using a design space (DS) plot. This plot uses Monte Carlo simulations for risk analysis, estimating the volume in the experimental design region where it can be expected that all specifications are fulfilled at a specific risk level. Figure 6 shows the DS plot using as specification a high LGO conversion (Y1 > 80%). However, it should be taken into account that the lower enzyme residual activity, the greater LGO conversion (>80%). Three points were identified using this plot. Point A is the optimum identified by a Nelder-Mead Simplex algorithm, Point B uses a lower enzyme loading to convert at least 80% of LGO (both with a risk level between 1 and 2%) and Point C illustrates a condition where no risk is taken to obtain 80% as minimum value for both responses, in spite of using a high enzyme loading.


Lipase-Catalyzed Baeyer-Villiger Oxidation of Cellulose-Derived Levoglucosenone into (S)-γ-Hydroxymethyl-α,β-Butenolide: Optimization by Response Surface Methodology.

Teixeira AR, Flourat AL, Peru AA, Brunissen F, Allais F - Front Chem (2016)

Design space plot. Contours indicate the risk of failure (%) in the specifications fulfilling (LGO conversion > 80%, pkaHEPES = 7.5). Green color indicates the area where the risk of failure is lower (< 1%), while the red indicates a higher risk of failure (> 2%). Point A- optimum identified by a Nelder-Mead Simplex algorithm (194 PLU.mmol-1 and [LGO] = 0.50 M), Point B - optimum identified in an earlier publication (Flourat et al., 2014) (113 PLU.mmol-1 and [LGO] = 0.75 M); Point C - point with a zero risk level (227 PLU.mmol-1 and [LGO] = 0.75 M).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4835721&req=5

Figure 6: Design space plot. Contours indicate the risk of failure (%) in the specifications fulfilling (LGO conversion > 80%, pkaHEPES = 7.5). Green color indicates the area where the risk of failure is lower (< 1%), while the red indicates a higher risk of failure (> 2%). Point A- optimum identified by a Nelder-Mead Simplex algorithm (194 PLU.mmol-1 and [LGO] = 0.50 M), Point B - optimum identified in an earlier publication (Flourat et al., 2014) (113 PLU.mmol-1 and [LGO] = 0.75 M); Point C - point with a zero risk level (227 PLU.mmol-1 and [LGO] = 0.75 M).
Mentions: Alternative optimal conditions can be explored using a design space (DS) plot. This plot uses Monte Carlo simulations for risk analysis, estimating the volume in the experimental design region where it can be expected that all specifications are fulfilled at a specific risk level. Figure 6 shows the DS plot using as specification a high LGO conversion (Y1 > 80%). However, it should be taken into account that the lower enzyme residual activity, the greater LGO conversion (>80%). Three points were identified using this plot. Point A is the optimum identified by a Nelder-Mead Simplex algorithm, Point B uses a lower enzyme loading to convert at least 80% of LGO (both with a risk level between 1 and 2%) and Point C illustrates a condition where no risk is taken to obtain 80% as minimum value for both responses, in spite of using a high enzyme loading.

Bottom Line: Response surface methodology (RSM), based on central composite face-centered (CCF) design, was employed to evaluate the factors effecting the enzyme-catalyzed reaction: pka of solid buffer (7.2-9.6), LGO concentration (0.5-1 M) and enzyme loading (55-285 PLU.mmol(-1)).Enzyme loading and pka of solid buffer were found to be important factors to the reaction efficiency (as measured by the conversion of LGO) while only the later had significant effects on the enzyme recyclability (as measured by the enzyme residual activity).A good agreement between experimental and predicted values was obtained and the model validity confirmed (p < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Chaire Agro-Biotechnologies Industrielles, AgroParisTechReims, France; UMR GENIAL, AgroParisTech, Institut National de la Recherche Agronomique, Université Paris-SaclayMassy, France.

ABSTRACT
Cellulose-derived levoglucosenone (LGO) has been efficiently converted into pure (S)-γ-hydroxymethyl-α,β-butenolide (HBO), a chemical platform suited for the synthesis of drugs, flavors and antiviral agents. This process involves two-steps: a lipase-catalyzed Baeyer-Villiger oxidation of LGO followed by an acid hydrolysis of the reaction mixture to provide pure HBO. Response surface methodology (RSM), based on central composite face-centered (CCF) design, was employed to evaluate the factors effecting the enzyme-catalyzed reaction: pka of solid buffer (7.2-9.6), LGO concentration (0.5-1 M) and enzyme loading (55-285 PLU.mmol(-1)). Enzyme loading and pka of solid buffer were found to be important factors to the reaction efficiency (as measured by the conversion of LGO) while only the later had significant effects on the enzyme recyclability (as measured by the enzyme residual activity). LGO concentration influences both responses by its interaction with the enzyme loading and pka of solid buffer. The optimal conditions which allow to convert at least 80% of LGO in 2 h at 40°C and reuse the enzyme for a subsequent cycle were found to be: solid buffer pka = 7.5, [LGO] = 0.50 M and 113 PLU.mmol(-1) for the lipase. A good agreement between experimental and predicted values was obtained and the model validity confirmed (p < 0.05). Alternative optimal conditions were explored using Monte Carlo simulations for risk analysis, being estimated the experimental region where the LGO conversion higher than 80% is fulfilled at a specific risk of failure.

No MeSH data available.


Related in: MedlinePlus