Analogs of S-Adenosyl-L-Methionine in Studies of Methyltransferases

Rudenko, A. Yu.; Mariasina, Sofia S.; Сергиев, Петр В.; Polshakov, Vladimir I.

doi:10.1134/s002689332202011x

Cited by 26 publications

(16 citation statements)

References 142 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since conventional MTs are able to transfer alternative alkyl chains such as ethyl (from L-Eth/SAE), [33–35] we wondered if radical SAM MTs such as QCMT would be able to generally catalyse alkyl transfer to the peptide substrate. Such an activity by class B radical SAM MTs would be highly interesting, as it would potentially enable the stereo- and regioselective introduction of new functionalities to sp 3 carbons via a radical mechanism.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Biomimetic S-Adenosylmethionine Regeneration Starting from Different Byproducts Enables Biocatalytic Alkylation with Radical SAM Enzymes

Gericke

Karst

Mhaindarkar

et al. 2022

Preprint

View full text Add to dashboard Cite

S-Adenosylmethionine (SAM) is an essential and versatile cofactor in nature. SAM-dependent enzymes, such as conventional methyltransferases (MTs), amino(carboxy)propyl transferases, and radical SAM enzymes, are of great interest as biocatalytic tools for chemical synthesis and the pharmaceutical industry. The use of SAM analogues adds to the diversity of reaction types and products. While SAM regeneration protocols for conventional MTs are available, in vitro SAM regeneration for polyamine-forming enzymes and radical SAM enzymes has not been solved yet. Here, we report a biomimetic cofactor regeneration cycle for three important types of SAM dependent enzymes featuring adenine as a central intermediate. SAM is regenerated from its main degradation products, S-adenosylhomocysteine, 5′ methylthioadenosine, and 5′-deoxyadenosine. We further show the chemical diversification of the system using SAM analogues such as S-adenosylethionine for MT reactions. Interestingly, the enzyme cascades also enable the transfer of an ethyl group with a cobalamin-dependent radical SAM MT. The possibility to regenerate SAM (analogues) for biocatalytic use with a broad range of enzymes will be a starting point for further application of the diverse chemistry accessible by SAM-based catalysis, as well as provide new options for mechanistic studies.

show abstract

Section: Resultsmentioning

confidence: 99%

“…MTs have been used together with alkyl analogues of SAM to transfer bulkier residues. [33–35] Radical SAM enzymes have been shown to support the cleavage of S -adenosylethionine (SAE) and S -adenosyl-L-allyl homocysteine as well as the transfer of various nucleosides to substrate analogues. [36–38]…”

Section: Introductionmentioning

confidence: 99%

Biomimetic S-Adenosylmethionine Regeneration Starting from Different Byproducts Enables Biocatalytic Alkylation with Radical SAM Enzymes

Gericke

Karst

Mhaindarkar

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In this study, the strategy of promoting SAM synthesis together with promoting the degradation of the byproduct SAH is more advantageous to SAM regeneration, thereby increasing the production of vanillin . As a universal biological cofactor, SAM also participates in the transfer of methyl groups during the synthesis of DNA, proteins, and small-molecule secondary metabolites . In biological systems, DNA methylation using SAM as a cofactor protects DNA from digestion .…”

Section: Discussionmentioning

confidence: 99%

Yeast-Based Whole-Cell Factory for the Ecofriendly Synthesis of Vanillylamine as a Critical Step toward Capsaicin Production

Zhao

et al. 2023

ACS Sustainable Chem. Eng.

View full text Add to dashboard Cite

Capsaicin is a biologically active alkaloid with important pharmaceutical, food, and cosmetic applications. As capsaicin production is dependent on its extraction from plants, its industrial separation and purification capacity is greatly limited. The chemical synthesis of capsaicin via the Schotten−Baumann reaction requires vanillylamine and 8-methyl-6-nonenoic acid as reaction substrates. Currently, petrochemical products obtained by the catalysis of precious metals are used to produce vanillylamine; however, this approach does not meet the requirements advocated by the green chemical industry. Herein, we developed an efficient yeast-based whole-cell factory for the de novo biosynthesis of vanillylamine and capsaicin. A heterologous recombinant vanillylamine biosynthetic pathway in yeast yielded 6.47 g/L vanillylamine. Enhancing the phenylalanine pool by upregulating the shikimic acid pathway led to an 11% increase in vanillylamine production. Optimization of methyl transfer efficiency via a reconstituted Sadenosylmethionine (SAM) circulating cycle resulted in an 84% increase in vanillylamine production. Switching the yeast strain from Z2 to Z6 and rewiring the precursor pool and SAM circulating cycle increased vanillylamine production to 14.89 g/L (125%)�the highest reported level in the current literature. Based on the biosynthesis of vanillylamine via the heterologous recombinant fatty acid pathway, capsaicin was synthesized de novo in yeast. We also revealed that protocatechuic acid can be produced from 3dehydroshikimic acid by phenylalanine ammonium lyase or tyrosine ammonia lyase. In summary, this study provides a feasible strategy for developing yeast-based whole-cell factories for the eco-friendly synthesis of vanillylamine, which is a critical step toward capsaicin production in yeast.

show abstract

“…S -adenosyl-L-methionine (SAM) is a cofactor for virtually all known RNA and DNA methyltransferases (MTases), which transfer the methyl group of SAM to the specific methylation sites [ 72 ]. Various SAM analogs have been synthesized and used to study the catalytic activity of MTases and identify new MTase substrates for more than two decades [ 73 ]. However, SAM derivatives are less stable under the ambient reaction conditions and are hard to be internalized through the cell membranes due to its nature with charge [ 74 ].…”

Section: Chemical Sequencing Methods For Detecting Rna Natural Modifi...mentioning

confidence: 99%

Determining RNA Natural Modifications and Nucleoside Analog-Labeled Sites by a Chemical/Enzyme-Induced Base Mutation Principle

Bao

Liu

2023

Molecules

View full text Add to dashboard Cite

The natural chemical modifications of messenger RNA (mRNA) in living organisms have shown essential roles in both physiology and pathology. The mapping of mRNA modifications is critical for interpreting their biological functions. In another dimension, the synthesized nucleoside analogs can enable chemical labeling of cellular mRNA through a metabolic pathway, which facilitates the study of RNA dynamics in a pulse-chase manner. In this regard, the sequencing tools for mapping both natural modifications and nucleoside tags on mRNA at single base resolution are highly necessary. In this work, we review the progress of chemical sequencing technology for determining both a variety of naturally occurring base modifications mainly on mRNA and a few on transfer RNA and metabolically incorporated artificial base analogs on mRNA, and further discuss the problems and prospects in the field.

show abstract

Analogs of S-Adenosyl-L-Methionine in Studies of Methyltransferases

Cited by 26 publications

References 142 publications

Biomimetic S-Adenosylmethionine Regeneration Starting from Different Byproducts Enables Biocatalytic Alkylation with Radical SAM Enzymes

Biomimetic S-Adenosylmethionine Regeneration Starting from Different Byproducts Enables Biocatalytic Alkylation with Radical SAM Enzymes

Yeast-Based Whole-Cell Factory for the Ecofriendly Synthesis of Vanillylamine as a Critical Step toward Capsaicin Production

Determining RNA Natural Modifications and Nucleoside Analog-Labeled Sites by a Chemical/Enzyme-Induced Base Mutation Principle

Contact Info

Product

Resources

About