Biocatalysis has found numerous applications in various fields as an alternative to chemical catalysis. The use of enzymes in organic synthesis, especially to make chiral compounds for pharmaceuticals as well for the flavors and fragrance industry, are the most prominent examples. In addition, biocatalysts are used on a large scale to make specialty and even bulk chemicals. This review intends to give illustrative examples in this field with a special focus on scalable chemical production using enzymes. It also discusses the opportunities and limitations of enzymatic syntheses using distinct examples and provides an outlook on emerging enzyme classes.

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Biocatalysis: Enzymatic Synthesis for Industrial Applications

For the planning of an organic synthesis route, the disconnection approach guided by retrosynthetic analysis of possible intermediates and the chemical reactions involved, back to ready available starting materials, is well established In contrast, such concepts just get developed for biocatalytic routes In this Review we highlight functional group interconversions catalyzed by enzymes The article is organized rather by chemical bonds formed-exemplified for C-N, C-O- and C-C-bonds-and not by enzyme classes, covering a broad range of reactions to incorporate the desired functionality in the target molecule Furthermore, the successful use of biocatalysts, also in combination with chemical steps, is exemplified for the synthesis of various drugs and advanced pharmaceutical intermediates such as Crispine A, Sitagliptin and Atorvastatin This Review also provides some basic guidelines to choose the most appropriate enzyme for a targeted reaction keeping in mind aspects like commercial availability, cofactor-requirement, solvent tolerance, use of isolated enzymes or whole cell recombinant microorganisms aiming to assist organic chemists in the use of enzymes for synthetic applications

https://onlinelibrary.wiley.com/doi/pdf/10.1002/chem.201702235

A Retrosynthesis Approach for Biocatalysis in Organic Synthesis.

Round, round we go - strategies for enzymatic cofactor regeneration.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ange.202006648

Biokatalyse: Enzymatische Synthese für industrielle Anwendungen

S-adenosylmethionine-dependent methyltransferases form a large family of enzymes that can catalyse regio-, chemo- and stereospecific methylation of complex natural products. These enzymes could be very useful tools for the chemoenzymatic production and diversification of natural or artificial compounds. Despite this potential, in vitro applications of methyltransferases are limited by their requirement for S-adenosylmethionine as a stoichiometric methyl donor. The chemical complexity, instability, high cost and poor atom economy of this reagent prevent preparative in vitro methylation reactions from becoming routine protocols in natural product research and viable options for process development. In this Article we demonstrate that C-, N- and O-specific methyltransferases can be combined with halide methyltransferases to form enzyme cascades that require only catalytic concentrations of S-adenosylmethionine and use methyl iodide as the stoichiometric methyl donor. Regenerating expensive S-adenosylmethionine (SAM) in enzymatic in vitro reactions is challenging—but important for the commercial scope of SAM-dependent enzymes. This work reports a simple two-enzyme cascade for the in vitro regeneration of SAM for the enzymatic methylation of diverse substrates.

/pdf/s-adenosylhomocysteine-as-a-methyl-transfer-catalyst-in-2s58oy9dmf.pdf

S-adenosylhomocysteine as a methyl transfer catalyst in biocatalytic methylation reactions

S-Adenosylmethionine-dependent methyltransferases (MTs) play a decisive role in the biosynthesis of natural products and in epigenetic processes. MTs catalyze the methylation of heteroatoms and even of carbon atoms, which, in many cases, is a challenging reaction in conventional synthesis. However, C-MTs are often highly substrate-specific. Herein, we show that SgvM from Streptomyces griseoviridis features an extended substrate scope with respect to the nucleophile as well as the electrophile. Aside from its physiological substrate 4-methyl-2-oxovalerate, SgvM catalyzes the (di)methylation of pyruvate, 2-oxobutyrate, 2-oxovalerate, and phenylpyruvate at the β-carbon atom. Chiral-phase HPLC analysis revealed that the methylation of 2-oxovalerate occurs with R selectivity while the ethylation of 2-oxobutyrate with S-adenosylethionine results in the S enantiomer of 3-methyl-2-oxovalerate. Thus SgvM could be a valuable tool for asymmetric biocatalytic C-alkylation reactions.

Christina Sommer-Kamann

Papers

Asymmetric C‐Alkylation by the S‐Adenosylmethionine‐Dependent Methyltransferase SgvM