Power of Biocatalysis for Organic Synthesis

Abstract

Biocatalysis, using defined enzymes for organic transformations, has become a common tool in organic synthesis, which is also frequently applied in industry. The generally high activity and outstanding stereo-, regio-, and chemoselectivity observed in many biotransformations are the result of a precise control of the reaction in the active site of the biocatalyst. This control is achieved by exact positioning of the reagents relative to each other in a fine-tuned 3D environment, by specific activating interactions between reagents and the protein, and by subtle movements of the catalyst. Enzyme engineering enables one to adapt the catalyst to the desired reaction and process. A well-filled biocatalytic toolbox is ready to be used for various reactions. Providing nonnatural reagents and conditions and evolving biocatalysts enables one to play with the myriad of options for creating novel transformations and thereby opening new, short pathways to desired target molecules. Combining several biocatalysts in one pot to perform several reactions concurrently increases the efficiency of biocatalysis even further.

Chromoselective Photocatalysis Enables Stereocomplementary Biocatalytic Pathways**

“…[5a] Here we show that electron holes with different oxidation potentials can be generated by using a heterogeneous carbon nitride (CN) catalyst by changing the incident photon energy. The combination of this strategy with two enantioselective biocatalysts [6] allowed us to selectively produce the (S)-or (R)-enantiomer of a chiral alcohol in photo-chemo-enzymatic reaction sequences (Scheme 1 C).…”

Recent trends in biocatalysis

“…333,344,345,364,365 P450s can execute an impressive variety of other reactions 340,[366][367][368] and were even engineered to perform a set of 'new-to-nature' reactions. [369][370][371][372] To direct the biological activity of steroid drugs, mainly their stereo-and regioselective hydroxylation activities are of interest. 344 To name two, a hydroxyl function at position 11b is required for the anti-inflammatory activity of cortisol and prednisolone 373 and the presence of two hydroxyl groups -1a and 25a -is essential for the biological activity of vitamin D derivatives.…”

“…405 These -to say at the least -modest performances of biocatalytic syntheses are a current and future challenge, not only of recombinant processes for steroid modifications. 372,409 To date, only two recombinant processes yielding steroidal APIs have been implemented industrially. Shi et al developed a process that converts CA to 12-oxo-CDCA, a key precursor for chemoenzymatic synthesis of UDCA, in a single step with very high productivity (68 g L À1 h À1 ).…”

“… 405 These – to say at the least – modest performances of biocatalytic syntheses are a current and future challenge, not only of recombinant processes for steroid modifications. 372,409 …”

Prospects of Using Biocatalysis for the Synthesis and Modification of Polymers

“…Important for an optimistic assessment of the prospects for the practical use of biocatalysis in new fields is the fact that many enzymes are able to efficiently convert not only their “natural” substrates, but also a wide range of synthetic organic compounds [ 12 , 13 , 14 , 15 ]. One of the areas of chemistry in which the possibility of using enzymes has been actively studied in recent decades is polymer chemistry.…”