Biocatalytic Friedel–Crafts Alkylation Using Non‐natural Cofactors

Stecher, Harald; Tengg, Martin; Ueberbacher, Bernhard J.; Remler, Peter; Schwab, Helmut; Griengl, Herfried; Gruber‐Khadjawi, Mandana

doi:10.1002/ange.200905095

Cited by 52 publications

(48 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[3,7] Other enzymatic C À C bond-forming reactions have just started to be investigated. [8] All of these enzymes are either lyases or transferases, but not redox enzymes. [9] In contrast, the berberine bridge enzyme (BBE) [EC 1.21.…”

mentioning

confidence: 99%

Biocatalytic Enantioselective Oxidative CC Coupling by Aerobic CH Activation

et al. 2011

View full text Add to dashboard Cite

mentioning

confidence: 99%

Biocatalytic Enantioselective Oxidative CC Coupling by Aerobic CH Activation

et al. 2011

View full text Add to dashboard Cite

“…Of the various MTs available, C‐MTs are particularly attractive as they enable C−C bond formation under conditions that are mild relative to those of traditional Friedel–Crafts reactions . One C‐MT exemplar is NovO, which methylates the C‐8 position of 1 a in the biosynthesis of the antibiotic novobiocin to form 2 a (Scheme A) .…”

Section: Methodsmentioning

confidence: 99%

A Tandem Enzymatic sp²‐C‐Methylation Process: Coupling in Situ S‐Adenosyl‐l‐Methionine Formation with Methyl Transfer

et al. 2017

View full text Add to dashboard Cite

A one-pot, two-step biocatalytic platform for the regiospecfic C-methylation and C-ethylation of aromatic substrates is described. The tandem process utilises SalL (Salinospora tropica) for in situ synthesis of S-adenosyl-l-methionine (SAM), followed by alkylation of aromatic substrates by the C-methyltransferase NovO (Streptomyces spheroides). The application of this methodology is demonstrated for the regiospecific labelling of aromatic substrates by the transfer of methyl, ethyl and isotopically labelled CH CD and CD groups from their corresponding SAM analogues formed in situ.

show abstract

“…Finally, the biocatalytic repertoire of small molecule MTases can be expanded with synthetic AdoMet analogues [41][42][43][44] . This represents a new approach to introduce structural diversity into natural products, e.g.…”

Section: Double Activated Cofactormentioning

confidence: 99%

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Hanz

Jung

Giesbertz

et al. 2014

JoVE

View full text Add to dashboard Cite

S-Adenosyl-l-methionine (AdoMet or SAM)-dependent methyltransferases (MTase) catalyze the transfer of the activated methyl group from AdoMet to specific positions in DNA, RNA, proteins and small biomolecules. This natural methylation reaction can be expanded to a wide variety of alkylation reactions using synthetic cofactor analogues. Replacement of the reactive sulfonium center of AdoMet with an aziridine ring leads to cofactors which can be coupled with DNA by various DNA MTases. These aziridine cofactors can be equipped with reporter groups at different positions of the adenine moiety and used for Sequence-specific Methyltransferase-Induced Labeling of DNA (SMILing DNA). As a typical example we give a protocol for biotinylation of pBR322 plasmid DNA at the 5'-ATCGAT-3' sequence with the DNA MTase M.BseCI and the aziridine cofactor 6BAz in one step. Extension of the activated methyl group with unsaturated alkyl groups results in another class of AdoMet analogues which are used for methyltransferase-directed Transfer of Activated Groups (mTAG). Since the extended side chains are activated by the sulfonium center and the unsaturated bond, these cofactors are called double-activated AdoMet analogues. These analogues not only function as cofactors for DNA MTases, like the aziridine cofactors, but also for RNA, protein and small molecule MTases. They are typically used for enzymatic modification of MTase substrates with unique functional groups which are labeled with reporter groups in a second chemical step. This is exemplified in a protocol for fluorescence labeling of histone H3 protein. A small propargyl group is transferred from the cofactor analogue SeAdoYn to the protein by the histone H3 lysine 4 (H3K4) MTase Set7/9 followed by click labeling of the alkynylated histone H3 with TAMRA azide. MTase-mediated labeling with cofactor analogues is an enabling technology for many exciting applications including identification and functional study of MTase substrates as well as DNA genotyping and methylation detection. Video LinkThe video component of this article can be found at

show abstract

Biocatalytic Friedel–Crafts Alkylation Using Non‐natural Cofactors

Cited by 52 publications

References 27 publications

Biocatalytic Enantioselective Oxidative CC Coupling by Aerobic CH Activation

Biocatalytic Enantioselective Oxidative CC Coupling by Aerobic CH Activation

A Tandem Enzymatic sp²‐C‐Methylation Process: Coupling in Situ S‐Adenosyl‐l‐Methionine Formation with Methyl Transfer

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Contact Info

Product

Resources

About

Biocatalytic Friedel–Crafts Alkylation Using Non‐natural Cofactors

Cited by 52 publications

References 27 publications

Biocatalytic Enantioselective Oxidative CC Coupling by Aerobic CH Activation

Biocatalytic Enantioselective Oxidative CC Coupling by Aerobic CH Activation

A Tandem Enzymatic sp2‐C‐Methylation Process: Coupling in Situ S‐Adenosyl‐l‐Methionine Formation with Methyl Transfer

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Contact Info

Product

Resources

About

A Tandem Enzymatic sp²‐C‐Methylation Process: Coupling in Situ S‐Adenosyl‐l‐Methionine Formation with Methyl Transfer