Asymmetric β‐Methylation of <scp>l</scp>‐ and <scp>d</scp>‐α‐Amino Acids by a Self‐Contained Enzyme Cascade

Liao, Cangsong; Seebeck, Florian P.

doi:10.1002/anie.201916025

Cited by 45 publications

(56 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[35] 4. Tandem enzymatic alkylation by using A) MAT, [9,[20][21]25,[37][38][39] B) an HMT-mediated SAM regeneration process, [40] and C) SalL to generate SAM analogues in situ.…”

Section: Development Of Sam Cofactor Regeneration Systemsmentioning

confidence: 99%

“…[b] Product prepared by a cyclic SAM regeneration process. [32,40] as demonstrated by regeneration cycles ranging from 35-290. Although, in its current guise, the enzymatic platform might be limited to in vitro applications with methyl iodide as the methylating agent, there exists distinct opportunities to engineer this platform to use much milder electrophilic agents, which could be compatible with in cell or lysate-based systems.…”

Section: Development Of Sam Cofactor Regeneration Systemsmentioning

confidence: 99%

“…[21,25,39,[47][48][49] The in situ synthesis of these cofactor analogues can then be used as substrates to transfer functional handles catalyzed by a variety of O- (14 a-d), C-(14 e) and N-(14 g) MTases (Figure 4a). [9,[20][21]25,[37][38][39] In addition, Seebeck et al expanded their two-enzyme SAM regeneration strategy (Figure 3B) [35] to stereoselectively prepare L-or D-β-alkylated αamino acids amino acids such as 14 f ( Figure 4B), [40] which are challenging to prepare by conventional chemical synthesis.…”

Section: Enhancing the Scope Of Biocatalytic Alkylation Using Modifiementioning

confidence: 99%

See 2 more Smart Citations

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late‐Stage Functionalization

2020

View full text Add to dashboard Cite

This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare Sadenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Second, innovative methods to regenerate SAM cofactors by enzymatic cascades is reported. Finally, future opportunities towards establishing a generalized platform for late-stage alkylation are described.

show abstract

“…[35] 4. Tandem enzymatic alkylation by using A) MAT, [9,[20][21]25,[37][38][39] B) an HMT-mediated SAM regeneration process, [40] and C) SalL to generate SAM analogues in situ.…”

Section: Development Of Sam Cofactor Regeneration Systemsmentioning

confidence: 99%

Section: Development Of Sam Cofactor Regeneration Systemsmentioning

confidence: 99%

Section: Enhancing the Scope Of Biocatalytic Alkylation Using Modifiementioning

confidence: 99%

See 1 more Smart Citation

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late‐Stage Functionalization

2020

View full text Add to dashboard Cite

show abstract

“…Recently, coupling of different enantioselective SAM-dependent α-keto acid methyltransferases (MT) with a halide methyltransferase (HMT) and a ω- or L -α-TA has been successfully applied for the synthesis of several enantio-enriched D - and L -β-methyl-α-AAs ( Supplementary Figure S3 , Liao and Seebeck, 2020 ). An S -adenosylhomocysteine nucleosidase-deficient E. coli strain was necessary for this approach, using CH 3 I as the alkylating agent.…”

Section: Multienzymatic Cascades For the Production Of Ncaasmentioning

confidence: 99%

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Martínez‐Rodríguez

Torres

Sánchez

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

The 22 genetically encoded amino acids (AAs) present in proteins (the 20 standard AAs together with selenocysteine and pyrrolysine), are commonly referred as proteinogenic AAs in the literature due to their appearance in ribosome-synthetized polypeptides. Beyond the borders of this key set of compounds, the rest of AAs are generally named imprecisely as non-proteinogenic AAs, even when they can also appear in polypeptide chains as a result of post-transductional machinery. Besides their importance as metabolites in life, many of D-α-and L-α-"non-canonical" amino acids (NcAAs) are of interest in the biotechnological and biomedical fields. They have found numerous applications in the discovery of new medicines and antibiotics, drug synthesis, cosmetic, and nutritional compounds, or in the improvement of protein and peptide pharmaceuticals. In addition to the numerous studies dealing with the asymmetric synthesis of NcAAs, many different enzymatic pathways have been reported in the literature allowing for the biosynthesis of NcAAs. Due to the huge heterogeneity of this group of molecules, this review is devoted to provide an overview on different established multienzymatic cascades for the production of non-canonical D-α-and L-α-AAs, supplying neophyte and experienced professionals in this field with different illustrative examples in the literature. Whereas the discovery of new or newly designed enzymes is of great interest, dusting off previous enzymatic methodologies by a "back and to the future" strategy might accelerate the implementation of new or improved multienzymatic cascades.

show abstract

“…Multi-enzyme catalysis that can run a series of reactions has drawn increasing attentions for the production of high-value chemicals in the past decade [1][2][3][4][5][6] . In this approach, cofactor recycling is fundamentally essential to drive reactions towards the desired direction 4,[7][8][9][10][11] . With respect to industrial biocatalysis, many enzyme processes rely on cofactors for their catalytic activity 7,12 .…”

Section: Introductionmentioning

confidence: 99%

Confining enzyme clusters in supramolecular nanoreactors enhances cofactor-dependent cascade for chiral alcohol synthesis

Zhang

Cao

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

Enzymes in living organisms work efficiently in confined environments through spatial organization. Constituting a bio-cascade reaction in nano-confined space in vitro for the efficient synthesis of high-value chiral chemicals is challenging. Herein, we confined a cofactor-dependent cascade in bacteriophage P22 nanoparticles for the synthesis of chiral alcohols. Compared to free enzymes, this supramolecular ensemble, P22-SP-BmGDH-SsCR, exhibited enhanced catalytic efficiency up to 14.5-fold towards various ketones and improved stereoselectivity up to > 99% ee towards 8 substrates, and 10 chiral alcohols with > 96% ee were synthesized. The recycling efficiency of nicotinamide adenine dinucleotide phosphate (NADPH) was increased by 7.5-fold. We demonstrated that the enhancement in cofactor recycling originates from the higher local concentration of NADPH in the nanoparticles due to the proximity effect of enzymes and confinement of nanoparticles. The preparative synthesis of chiral alcohols showed that the consumption of NADPH can be reduced by one magnitude compared with the conventional free enzyme system.

show abstract

Asymmetric β‐Methylation of l‐ and d‐α‐Amino Acids by a Self‐Contained Enzyme Cascade

Cited by 45 publications

References 53 publications

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late‐Stage Functionalization

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late‐Stage Functionalization

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

Confining enzyme clusters in supramolecular nanoreactors enhances cofactor-dependent cascade for chiral alcohol synthesis

Contact Info

Product

Resources

About