About this Research Topic
Small molecules identified from natural sources have served for decades as leads for the development of active, stable, and cheap pharmaceuticals. The golden age for the discovery of novel bioactive natural products spanned the 70s and 80s of the past century. However, the number of new natural scaffolds identified is approaching saturation, raising the need to further extend the diversity of small molecules inspired by Nature. Organochemical synthesis, molecular dissection, and other semi-synthetic approaches employed versatile techniques to achieve the latter purpose. Concurrently, utilization of greener and more sustainable biocatalytic approaches remained lagging. However, the recent revolution in the availability of genetic data, bioinformatics, and protein engineering technologies dramatically increased the repertoire of available enzymatic tools. Thus, enabling researchers to explore new territories of biocatalytic reactions. Additionally, biocatalysis is characterized by remarkable regio- and stereoselectivities that could not be easily achieved through conventional chemical methods.
So far, a major focus of biocatalysis has been devoted to mimicking nature for the biosynthesis of natural products, while less interest has been given to the modification of those natural products by enzymes not originally involved in their biosynthetic pathways. However, the emergence of the field of combinatorial biosynthesis incited the utilization of enzymes or cells to produce natural product analogues, generating new pools of small molecules with novel activities and/or enhanced properties. Additionally, the introduction of new functionalities less represented in nature, for example by halogenation, amination, or sulfation would greatly increase the diversity of the modified small molecules. The goal of this research topic is to broaden the current scope of biocatalytic synthetic tools for the modification of lead natural small molecules aiming at improving their bioactivities.
This Research Topic is open for both Original Research and Review articles focusing on the enzymatic modification of small molecules produced by living organisms. The aim is to produce functionalized potentially bioactive small molecules in enzyme-substrate combinations not known to nature so far. The modification may be achieved either in vitro or in vivo. Semisynthetic approaches involving chemo-bio or bio-chemo cascades also fall within the scope of the Research Topic if the modified small molecules have a natural origin. Areas to be covered in this Research Topic may include, but are not limited to:
• Enzymatic modification of natural small molecules preferentially using enzymes not known to be involved in their biosynthesis.
• Utilizing whole-cell biocatalysis to produce new natural products analogues.
• Enzymatic synthesis of pseudo-natural products.
• Cascade reactions involving enzymes aiming at the production of modified natural products, including chemo-enzymatic cascades.
• Protein engineering to modify the substrate and/or product scopes of biosynthetic enzymes to produce modified natural products.
• Combinatorial genetics for the biocatalytic synthesis of new scaffolds of small molecules.
So far, a major focus of biocatalysis has been devoted to mimicking nature for the biosynthesis of natural products, while less interest has been given to the modification of those natural products by enzymes not originally involved in their biosynthetic pathways. However, the emergence of the field of combinatorial biosynthesis incited the utilization of enzymes or cells to produce natural product analogues, generating new pools of small molecules with novel activities and/or enhanced properties. Additionally, the introduction of new functionalities less represented in nature, for example by halogenation, amination, or sulfation would greatly increase the diversity of the modified small molecules. The goal of this research topic is to broaden the current scope of biocatalytic synthetic tools for the modification of lead natural small molecules aiming at improving their bioactivities.
This Research Topic is open for both Original Research and Review articles focusing on the enzymatic modification of small molecules produced by living organisms. The aim is to produce functionalized potentially bioactive small molecules in enzyme-substrate combinations not known to nature so far. The modification may be achieved either in vitro or in vivo. Semisynthetic approaches involving chemo-bio or bio-chemo cascades also fall within the scope of the Research Topic if the modified small molecules have a natural origin. Areas to be covered in this Research Topic may include, but are not limited to:
• Enzymatic modification of natural small molecules preferentially using enzymes not known to be involved in their biosynthesis.
• Utilizing whole-cell biocatalysis to produce new natural products analogues.
• Enzymatic synthesis of pseudo-natural products.
• Cascade reactions involving enzymes aiming at the production of modified natural products, including chemo-enzymatic cascades.
• Protein engineering to modify the substrate and/or product scopes of biosynthetic enzymes to produce modified natural products.
• Combinatorial genetics for the biocatalytic synthesis of new scaffolds of small molecules.
Keywords: Biocatalytic Synthetic Tools, Sustainable biocatalytic approaches, Whole-cell biocatalysis, Combinatorial biosynthesis, Natural products analogues, Bioactive natural products, Protein engineering, Pseudo-natural products, Cascade reactions, Enzymology
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.
