Research Topic

Novel Strategies on Biocatalytic Alkylation of Small Molecules for Industrial Applications

About this Research Topic

Methylation of natural products dramatically changes the properties and the biological activity of compounds and is thus of extreme interest, yet often difficult to achieve by chemical synthesis. Over the last few years, small-molecule directed methyltransferases have drawn considerable interest in the biocatalysis community, especially after the development of the first regeneration cascades for the methyl donor, S-adenosyl-L-methionine (SAM), to overcome the economic challenge of such a bioprocess. Recently also other SAM-dependent alkylating enzymes and synthetic alkyl donors have gained attention in the field and are more and more investigated mechanistically. This emerging field of enzymatic alkylation is highly relevant to medicinal chemistry, biocatalysis and metabolic engineering and is currently undergoing a rapid expansion in the directions of enzyme discovery, elucidation of catalytic mechanisms and enzyme specificity, as well as co-factor synthesis and regeneration. These developments will lead to higher product yields and more efficient bioprocesses.

Current limitations for the development of efficient bioprocesses involving alkylating enzymes are the selection of the appropriate enzymes and the provision/recycling of the alkyl-donating cofactor. Several avenues towards overcoming these hurdles are currently explored including the mechanistic study of alkylating enzymes to establish sequence-to-function and structure-to-function relationships that facilitate the rational selection of enzymes from a range of candidates, prototyping strategies to screen enzyme libraries, as well as enzyme engineering and directed evolution approaches. Furthermore, engineering of enzymatic cascades for cofactor recycling in vivo and in vitro, as well as the design and synthesis of alternative alkyl-donors are highly promising approaches.

The aim of the current Research Topic is to cover promising, recent, and novel research trends in the field of natural product alkylation. This collection will provide a broad overview of the ongoing research in small molecule alkylation and provide a strong basis for the further expansion of the field. We welcome Original Research, Methods, Reviews, Mini Reviews, and Brief Research Reports.

Areas to be covered in this Research Topic may include, but are not limited to:
- enzyme discovery
- sequence-function and structure-function relationships of alkylating enzymes
- enzymatic alkylation cascades
- natural and recombinant pathways involving alkylating enzymes
- enzyme engineering and directed evolution towards novel substrate specificities of alkylating enzymes
- in vivo co-factor regeneration systems
- in vitro co-factor regeneration systems
- chemical co-factor regeneration systems
- synthesis of alternative alkyl-donors


Keywords: Alkylation, methyltransferase, S-adenosyl-L-methionine, Regeneration Cascade


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Methylation of natural products dramatically changes the properties and the biological activity of compounds and is thus of extreme interest, yet often difficult to achieve by chemical synthesis. Over the last few years, small-molecule directed methyltransferases have drawn considerable interest in the biocatalysis community, especially after the development of the first regeneration cascades for the methyl donor, S-adenosyl-L-methionine (SAM), to overcome the economic challenge of such a bioprocess. Recently also other SAM-dependent alkylating enzymes and synthetic alkyl donors have gained attention in the field and are more and more investigated mechanistically. This emerging field of enzymatic alkylation is highly relevant to medicinal chemistry, biocatalysis and metabolic engineering and is currently undergoing a rapid expansion in the directions of enzyme discovery, elucidation of catalytic mechanisms and enzyme specificity, as well as co-factor synthesis and regeneration. These developments will lead to higher product yields and more efficient bioprocesses.

Current limitations for the development of efficient bioprocesses involving alkylating enzymes are the selection of the appropriate enzymes and the provision/recycling of the alkyl-donating cofactor. Several avenues towards overcoming these hurdles are currently explored including the mechanistic study of alkylating enzymes to establish sequence-to-function and structure-to-function relationships that facilitate the rational selection of enzymes from a range of candidates, prototyping strategies to screen enzyme libraries, as well as enzyme engineering and directed evolution approaches. Furthermore, engineering of enzymatic cascades for cofactor recycling in vivo and in vitro, as well as the design and synthesis of alternative alkyl-donors are highly promising approaches.

The aim of the current Research Topic is to cover promising, recent, and novel research trends in the field of natural product alkylation. This collection will provide a broad overview of the ongoing research in small molecule alkylation and provide a strong basis for the further expansion of the field. We welcome Original Research, Methods, Reviews, Mini Reviews, and Brief Research Reports.

Areas to be covered in this Research Topic may include, but are not limited to:
- enzyme discovery
- sequence-function and structure-function relationships of alkylating enzymes
- enzymatic alkylation cascades
- natural and recombinant pathways involving alkylating enzymes
- enzyme engineering and directed evolution towards novel substrate specificities of alkylating enzymes
- in vivo co-factor regeneration systems
- in vitro co-factor regeneration systems
- chemical co-factor regeneration systems
- synthesis of alternative alkyl-donors


Keywords: Alkylation, methyltransferase, S-adenosyl-L-methionine, Regeneration Cascade


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

15 September 2021 Abstract
31 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

15 September 2021 Abstract
31 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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