Industrial biotransformations in the synthesis of building blocks leading to enantiopure drugs

Solano, D. Muñoz; Hoyos, Pilar; Hernáiz, María J.; Alcántara, A.R.; Sánchez-Montero, J.M.

doi:10.1016/j.biortech.2011.11.131

Cited by 185 publications

(59 citation statements)

References 54 publications

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“…Application of microbial enzymes or whole cells permits transformation with high chemo-, regio-, and enantioselectivity [7]. Notably, biotransformation is an environmentally friendly process because it can be conducted under mild conditions, requires few chemicals, and produces little toxic chemical waste.…”

Section: Introductionmentioning

confidence: 99%

Microbial Kinetic Resolution of Aroma Compounds Using Solid-State Fermentation

et al. 2018

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A novel microbial approach to the production of enantiomerically enriched and pure aroma compounds based on kinetic resolution via solid-state fermentation is proposed. Twenty-five filamentous fungi were screened for lipase activity and enantioselective hydrolysis of a volatile racemic ester (1-phenylethyl acetate (1)) and several racemic lactones (trans and cis whisky lactones (4, 5), γ-decalactone (7), δ-decalactone (8), (cis-3a,4,7,7a-tetrahydro-1(3H)-isobenzofuranone) (9)). Solid-state fermentation was conducted with linseed and rapeseed cakes. Kinetic resolution afforded enantiomerically enriched products with high enantiomeric excesses (ee = 82-99%). The results highlight the potential economic value of solid-state fermentation using agroindustrial side-stream feedstocks as an alternative to more expensive processes conducted in submerged fermentation.

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Section: Introductionmentioning

confidence: 99%

Microbial Kinetic Resolution of Aroma Compounds Using Solid-State Fermentation

et al. 2018

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“…The biotechnological potential and capabilities of nitrilases have been unmistakable, facilitating the move toward green chemistry within both the pharmaceutical and biotechnological industries (Gong et al, 2012;Martínková & Kren, 2010;Martínková et al, 2009;Sandhya et al, 2005;Singn et al, 2006;Solano et al, 2012;Robertson et al, 2004;Winkler et al, 2009). Environmental samples are continuously exploited for the isolation and identification of novel nitrilase enzymes, with the first plant and bacterial nitrilases identified in 1958 and 1964, respectively, (Robinson & Hook, 1964;Thimann & Mahadevan, 1958).…”

Section: Introductionmentioning

confidence: 99%

The use of clade‐specific PCR assays to identify novel nitrilase genes from environmental isolates

et al. 2018

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Nitrilase enzymes (EC 3.5.5.1) are responsible for the direct hydration of nitriles to their corresponding carboxylic acids and ammonia. The utilization of nitrilase enzymes in biocatalysis toward bio‐pharmaceuticals and industrial applications facilitates the move towards green chemistry. The body of research presented describes a novel clade‐specific touchdown PCR protocol for the detection of novel nitrilase genes. The presented study identified partial sequences of 15 novel nitrilase genes across 7 genera, with partial DNA sequence homology (%) displayed across an additional 16 genera. This research will prove valuable in the screening of microorganisms for the identification of novel clade‐specific nitrilase genes, with predicted enantioselective profiles as determined by their clade characterizations.

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“…Then, one alcohole nantiomer is acylated by an acyl donor and the other alcohol enantiomer is enriched.T he enantioselectivity of the transacylation reactionc an be controlled by using either R-o rS-selective en-zymes,s uch as R-selective lipases or S-selective serine proteases. [4,5] For R-selective KR reactions, Candida antarctica lipase B (CalB, Novozyme4 35) is commonly applied. For S-selective KR reactions, subtilisin Carlsberg (SC) and CalB W104Aa re used.…”

Section: Introductionmentioning

confidence: 99%

Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering

2017

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Generally, the catalytic activity of subtilisin Carlsberg (SC) for transacylation reactions with secondary alcohols in organic solvent is low. Enzyme immobilization and protein engineering was performed to improve the enantioselectivity of SC towards secondary alcohols. Possible amino-acid residues for mutagenesis were found by combining available literature data with molecular modeling. SC variants were created by site-directed mutagenesis and were evaluated for a model transacylation reaction containing 1-phenylethanol in THF. Variants showing high E values (>100) were found. However, the conversions were still low. A second mutation was made, and both the E values and conversions were increased. Relative to that shown by the wild type, the most successful variant, G165L/M221F, showed increased conversion (up to 36 %), enantioselectivity (E values up to 400), substrate scope, and stability in THF.

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Industrial biotransformations in the synthesis of building blocks leading to enantiopure drugs

Cited by 185 publications

References 54 publications

Microbial Kinetic Resolution of Aroma Compounds Using Solid-State Fermentation

Microbial Kinetic Resolution of Aroma Compounds Using Solid-State Fermentation

The use of clade‐specific PCR assays to identify novel nitrilase genes from environmental isolates

Improved Enantioselectivity of Subtilisin Carlsberg towards Secondary Alcohols by Protein Engineering

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