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Oxidation reactions catalysed by O2‐dependent enzymes are gaining increasing interest in the chemical industry due to their potential to provide a more selective and sustainable alternative to conventional chemical oxidation methods. O2‐dependent enzymes, like oxidases and oxygenases, catalyse a versatile range of oxidative reactions using only molecular oxygen as an oxidant. However, their practical application on a larger scale has been limited up to this point, primarily due to factors like their low catalytic rates combined with a narrow substrate spectrum and low stability. Nonetheless, enzyme engineering studies have significantly addressed these challenges in recent years and moved O2‐dependent enzymes closer towards industrial utilisation. This review aims to concisely overview the most recent engineering approaches to O2‐dependent enzymes. We will highlight recent studies that have targeted various aspects of O2‐dependent enzymes, including activity, selectivity, stability, and substrate spectrum, focusing on engineering studies where the engineered enzymes catalysed synthetically valuable reactions. [ABSTRACT FROM AUTHOR]

Pyrrole‐2,5‐dicarboxylic acid (PDCA) is a heterocyclic aromatic dicarboxylic acid that may emerge as a new monomer for polyester production. Compared to its structurally related and bio‐based furan‐2,5‐dicarboxylic acid (FDCA) that is already used for the production of polyethylene furanoate (PEF), PDCA shows excellent potential as its nitrogen can be targeted for further derivatization, thus enabling tuning of the properties of a PDCA containing polymer. In light of this, we recognized the need to explore efficient synthetic approaches for producing PDCAs in high yields. Here, we report a five‐step synthesis route for N‐substituted PDCAs starting from pyrrole, with total yields up to 42 %. The synthetic approach allowed the introduction of several different functional moieties to the pyrrole nitrogen, such as aliphatic saturated and unsaturated side‐chains, as well as benzylic groups. [ABSTRACT FROM AUTHOR]

Since the chemical industry is largely dependent on petrol‐based feedstocks, new sources are required for a sustainable industry. Conversion of biomass to high‐value compounds provides an environmentally friendly and sustainable approach, which might be a potential solution to reduce petrol‐based starting materials. This also applies for N‐heterocycles, which are a common structural motif in natural products, pharmaceuticals and functional polymers. The synthesis of pyrroles is a well‐studied and established process. Nevertheless, most routes described are not in line with the principles of green and sustainable chemistry and employ harsh reaction conditions and harmful solvents. In this study, 3,4‐dihydroxyketons are used as excellent platform chemicals for the production of N‐substituted pyrrole‐2‐carboxylic‐ and pyrrole‐2,5‐dicarboxylic acids, as they can be prepared from glucose through the intermediate d‐glucarate and converted into pyrrolic acid derivatives under mild conditions in water. The scope of this so far unknown reaction was examined using a variety of primary amines and aqueous ammonium chloride leading to pyrrolic acid derivatives with N‐substituents like alkane‐, alkene‐, phenyl‐ and alcohol‐groups with yields up to 20 %. The combination of both, enzymatic conversion and chemical reaction opens up new possibilities for further process development. Therefore, a continuous chemo‐enzymatic system was set up by first employing an immobilized enzyme to catalyze the conversion of d‐glucarate to the 3,4‐dihydroxyketone, which is further converted to the pyrrolic acid derivatives by a chemical step in continuous flow. [ABSTRACT FROM AUTHOR]

Having identified inconsistencies when repeating literature examples of photochemical transformations and difficulties recreating experimental setups, we devised several criteria that an ideal lab‐scale reactor should achieve. Herein, we introduce a versatile photoreactor for high‐throughput screening, preparative‐scale batch reactions and continuous processing, all with a single light source. The reactor utilizes interchangeable arrays of pseudo‐monochromatic high‐power LEDs in a range of synthetically useful wavelengths, combined with excellent temperature control. Moreover, light intensity can be modulated in an accurate and straightforward manner. This system has subsequently been tested on a range of literature methodologies. [ABSTRACT FROM AUTHOR]

The concurrent operation of chemical and biocatalytic reactions in one pot is still a challenging task, and, in particular for chemical photocatalysts, examples besides simple cofactor recycling systems are rare. However, especially due to the complementary chemistry that the two fields of catalysis promote, their combination in one pot has the potential to unlock intriguing, unprecedented overall reactivities. Herein we demonstrate a concurrent biocatalytic reduction and photocatalytic oxidation process. Specifically, the enantioselective biocatalytic sulfoxide reduction using (S)-selective methionine sulfoxide reductases was coupled to an unselective light-dependent sulfoxidation. Protochlorophyllide was established as a new green photocatalyst for the sulfoxidation. Overall, a cyclic deracemization process to produce nonracemic sulfoxides was achieved and the target compounds were obtained with excellent conversions (up to 91 %) and superb optical purity (>99 % ee)., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Biocatalysis, using enzymes for organic synthesis, has emerged as powerful tool for the synthesis of active pharmaceutical ingredients (APIs). The first industrial biocatalytic processes launched in the first half of the last century exploited whole-cell microorganisms where the specific enzyme at work was not known. In the meantime, novel molecular biology methods, such as efficient gene sequencing and synthesis, triggered breakthroughs in directed evolution for the rapid development of process-stable enzymes with broad substrate scope and good selectivities tailored for specific substrates. To date, enzymes are employed to enable shorter, more efficient, and more sustainable alternative routes toward (established) small molecule APIs, and are additionally used to perform standard reactions in API synthesis more efficiently. Herein, large-scale synthetic routes containing biocatalytic key steps toward >130 APIs of approved drugs and drug candidates are compared with the corresponding chemical protocols (if available) regarding the steps, reaction conditions, and scale. The review is structured according to the functional group formed in the reaction.

Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photo-chemo-enzymatic cascades that give either the (S)- or the (R)-enantiomer of phenylethanol. In combination with an unspecific peroxygenase from Agrocybe aegerita, green light irradiation of CN-OA-m led to the enantioselective hydroxylation of ethylbenzene to (R)-1-phenylethanol (99 % ee). In contrast, blue light irradiation triggered the photocatalytic oxidation of ethylbenzene to acetophenone, which in turn was enantioselectively reduced with an alcohol dehydrogenase from Rhodococcus ruber to form (S)-1-phenylethanol (93 % ee)., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)