Biocatalysis making waves in organic chemistry

Hanefeld, Ulf; Hollmann, Frank; Paul, Caroline E.

doi:10.1039/d1cs00100k

Cited by 157 publications

(90 citation statements)

References 363 publications

(425 reference statements)

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“…In biological systems, MTs [8] use the co‐substrate SAM as an electrophilic methyl donor (Scheme 1). Several problems limiting the use of SAM as a cofactor in synthetic methylation applications need to be overcome.…”

Section: Introductionmentioning

confidence: 99%

“…These are the features required for selective synthesis, and therefore, MTs are potentially industrially relevant for the synthesis of active pharmaceutical ingredients (APIs). [1,7] In biological systems, MTs [8] use the co-substrate SAM as an electrophilic methyl donor (Scheme 1). Several problems limiting the use of SAM as a cofactor in synthetic methylation applications need to be overcome.…”

Section: Introductionmentioning

confidence: 99%

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Methyltransferases: Functions and Applications

et al. 2022

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In this review the current state-of-the-art of S-adenosylmethionine (SAM)-dependent methyltransferases and SAM are evaluated. Their structural classification and diversity is introduced and key mechanistic aspects presented which are then detailed further. Then, catalytic SAM as a target for drugs, and approaches to utilise SAM as a cofactor in synthesis are introduced with different supply and regeneration approaches evaluated. The use of SAM analogues are also described. Finally O-, N-, C-and S-MTs, their synthetic applications and potential for compound diversification is given.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Methyltransferases: Functions and Applications

et al. 2022

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“…Using the example of oxyfunctionalisation enzymes such as cytochrome P450 monooxygenases (P450s), [51,52] unspecific peroxygenases (UPOs), [53,54] flavin‐dependent monooxygenases, [55,56] Rieske dioxygenases, [57,58] and αKGDs, [59,60] this perspective complements recent cutting‐edge biocatalysis review articles [2,14,16,17,61,62] in order to aid the transition towards sustainable chemistry by wide‐spread combinations of chemo‐ and biocatalysis [63–66] . Many of the here presented examples do not involve commercial enzyme kits yet, but rather self‐generated mutant libraries.…”

Section: Introductionmentioning

confidence: 96%

“…Importantly, enzyme kits can be easily and reproducibly applied, even by scientists unexperienced in biocatalysis. The principle of synthetic "First Aid" by enzyme kits is illustrated by three examples in Figure 1: A) Regiospecific early-and late-stage functionalisation in total synthesis by screening enzymes or mutant libraries [47,48] B) One-step late-stage functionalisation at different positions by a single promiscuous enzyme or mutant libraries [49] C) Chemoenzymatic late-stage diversification of substrates by mutant libraries and subsequent chemical modifications [50] Using the example of oxyfunctionalisation enzymes such as cytochrome P450 monooxygenases (P450s), [51,52] unspecific peroxygenases (UPOs), [53,54] flavin-dependent monooxygenases, [55,56] Rieske dioxygenases, [57,58] and αKGDs, [59,60] this perspective complements recent cutting-edge biocatalysis review articles [2,14,16,17,61,62] in order to aid the transition towards sustainable chemistry by wide-spread combinations of chemoand biocatalysis. [63][64][65][66] Many of the here presented examples do not involve commercial enzyme kits yet, but rather selfgenerated mutant libraries.…”

Section: Introductionmentioning

confidence: 99%

Enzyme Kits to Facilitate the Integration of Biocatalysis into Organic Chemistry – First Aid for Synthetic Chemists

2022

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First Aid Kits are collections of the most important medical equipment required for quick medical assistance. Similarly, enzyme kits can provide a proficient, ready-and easy-to-use collection of biocatalysts that can be applied with high reproducibility. In this article, we illustrate how kits of oxyfunctionalisation enzymes could operate as synthetic 'First Aid' for chemists working on complex natural product total synthesis in an early-or late-stage fashion, as well as in lead diversification in drug discovery processes. We reason that enzyme kits could catalyse the integration of biocatalysis into (synthetic) organic chemistry and describe how we envision their future application.

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“…4,5 Akin to photocatalysis, biocatalysis has been shown to enable sustainable reaction methodologies due to its generally mild reaction conditions, use of aqueous media, high stereo-and chemoselectivity, and ever-increasing substrate and reaction scope. [6][7][8][9][10][11][12][13] At the interface of these two fields of catalysis, photobiocatalysis arose, whereby either the enzyme itself requires light (naturally or by promiscuity) or photoinduced electrons are transferred to it. [14][15][16][17] The scope of photobiocatalytic transformations was significantly expanded following the discovery of fatty-acid photodecarboxylases in 2017.…”

Section: Introductionmentioning

confidence: 99%

Strategies for Transferring Photobiocatalysis to Continuous Flow Exemplified by the Photodecarboxylation of Fatty Acids

Simić

Jakštaitė

Huck

et al. 2022

Preprint

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The challenges of light-dependent biocatalytic transformations of lipophilic substrates in aqueous media are manifold. For instance, photolability of the catalyst as well as insufficient light penetration into the reaction vessel may be further exacerbated by a heterogeneously dispersed substrate. Light penetration may be addressed by performing the reaction in continuous flow, which allows two modes of applying the catalyst: (i) heterogenously, immobilized on a carrier, which requires light-permeable supports, or (ii) homogenously, dissolved in the reaction mixture. Taking the light-dependent photodecarboxylation of palmitic acid catalyzed by the fatty-acid photodecarboxylase from Chlorella variabilis (CvFAP) as a showcase, strategies for the transfer of a photoenzyme-catalyzed reaction into continuous flow were identified. A range of different supports was evaluated for the immobilization of CvFAP, whereby Eupergit C250 L was the carrier of choice. As the photostability of the catalyst was a limiting factor, a homogeneous system was preferred instead of employing the heterogenized enzyme. This implied that photolabile enzymes may preferably be applied in solution if repair mechanisms cannot be provided. Furthermore, when comparing different wavelengths and light intensities, extinction coefficients may be considered to ensure comparable absorption at each wavelength. Employing homogenous conditions in the CvFAP-catalyzed photodecarboxylation of palmitic acid afforded a space-time yield unsurpassed by any reported batch process (5.7 g/L·h, 26.9 mmol/L·h) for this reaction, demonstrating the advantage of continuous flow in attaining higher productivity of photobiocatalytic processes.

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Biocatalysis making waves in organic chemistry

Abstract: The many waves of biocatalysis have arisen to solve long-standing synthetic challenges. From industrially applied hydrolases to enzymes catalysing selective C–C-bond formation, biocatalysis enables new tools to access a plethora of compounds.

Cited by 157 publications

References 363 publications

Methyltransferases: Functions and Applications

Methyltransferases: Functions and Applications

Enzyme Kits to Facilitate the Integration of Biocatalysis into Organic Chemistry – First Aid for Synthetic Chemists

Strategies for Transferring Photobiocatalysis to Continuous Flow Exemplified by the Photodecarboxylation of Fatty Acids

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