An Artificial In Vitro Metabolism to Angiopterlactone B Inspired by Traditional Retrosynthesis
Alexander F Kiefer1, Yu-Chang Liu2,1, Rebecca Gummerer1
1Aalto University, Department of Chemistry, Kemistintie 1, 02150, Espoo, Finland.
Angewandte Chemie (International Ed. in English)
|March 20, 2023
Summary
This study introduces artificial metabolism by integrating non-natural biocatalytic modules. This novel approach enables efficient, two-step synthesis of complex molecules like angiopterlactone B in water using enzymes.
Area of Science:
- Biocatalysis and Synthetic Chemistry
- Metabolic Engineering
- Organic Synthesis
Background:
- Biosynthesis offers unparalleled complexity but limited scope.
- Chemical synthesis provides broad scope but lacks biosynthetic elegance.
- Integrating enzymatic and synthetic strategies is a key challenge.
Purpose of the Study:
- To develop an artificial metabolism combining biocatalysis and chemical synthesis.
- To incorporate non-natural enzymatic modules into a synthetic pathway.
- To achieve efficient synthesis of complex natural products.
Main Methods:
- Incorporation of a peroxidase-mediated Achmatowicz rearrangement.
- Integration of a dehydrogenase-catalyzed borrowing-hydrogen-type isomerization.
- Development of a two-step aqueous synthesis pathway.
Main Results:
- Successful integration of non-natural biocatalytic modules into an artificial metabolism.
- Streamlined, two-step total synthesis of tricyclic angiopterlactone B.
- Synthesis achieved entirely in an aqueous environment using enzymes.
Conclusions:
- Artificial metabolism can bridge the gap between biosynthesis and chemical synthesis.
- Enzyme-mediated reactions offer an efficient and environmentally friendly synthetic approach.
- This strategy enables the streamlined synthesis of complex molecular structures.
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