4 research outputs found

    Smart engineering of various enzymes for asymmetric synthesis of chiral molecules on industrial scale

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    The commercialization of sustainable enzymatic and microbial catalysis technology is gaining increasing priority for the synthesis of chiral compounds from achiral precursors that require high selectivity and high substrate load. Thus, the fast and cost-effective development of novel biocatalytic processes using an integrated platform offers significant opportunities to fine chemical, pharmaceutical, food & feed, material and related industries. Please click Additional Files below to see the full abstract

    Sustainable biocatalytic synthesis of β-hydroxyl-α-amino acids on an industrial scale

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    The development and commercialization of sustainable enzymatic and microbial catalysis technologies is gaining increasing priority to reduce the environmental impact of chemical and related industries. Enzymes offer, as common platform, significant opportunities for innovations to enhance production capabilities to meet these new reduced impact demands, whilst retaining product quality and keeping costs down. To enable cost efficient biocatalytic processes, however, high selectivity, high activity, high substrate loadings and tolerance to organic solvents are required. This is in general not sufficiently displayed by natural enzymes, despite providing high selectivity and activity on native substrates under physiological conditions. As a solution, enzyme engineering allows us to optimize any enzyme to a powerful catalyst that overcomes these boundaries and can be conveniently applied under industrial conditions. As an industrial example, we will discuss the synthesis of β-hydroxyl-α-amino acids, important chiral building blocks in pharmaceutical and fine chemical industry. Current chemical synthesis protocols employ hazardous and environmentally unfriendly methods, thus, a replacement by safe and green biocatalysis is desired. However, wild type aldolases do not meet the anticipated target criteria for selectivity, activity and solvent tolerance under process conditions. Nonetheless, smart bioinformatics guided directed evolution, enabled us to develop an enzyme variant which meets the industrial target for the sustainable (βR)-β-Hydroxy-4-nitro-L-phenylalanine production at multi ton scale, which is a precursor for chloramphenicol. Remarkably, this new synthetic route to chloramphenicol, enabled by our engineered aldolase, is 5 steps shorter than the traditional chemical route, avoiding the use of various hazardous and environmentally unfriendly reactants. Please click Additional Files below to see the full abstract

    Synthesis of guanidino analogues as potential nitric oxide synthase inhibitors

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    Baeyer–Villiger Monooxygenase-Mediated Synthesis of Esomeprazole As an Alternative for Kagan Sulfoxidation

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    A wild-type Baeyer–Villiger monooxygenase was engineered to overcome numerous liabilities in order to mediate a commercial oxidation of pyrmetazole to esomeprazole, using air as the terminal oxidant in an almost exclusively aqueous reaction matrix. The developed enzyme and process compares favorably to the incumbent Kagan inspired chemocatalytic oxidation, as esomeprazole was isolated in 87% yield, in >99% purity, with an enantiomeric excess of >99%
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