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Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions
Published on: November 30, 2022
Genetically programmed chiral organoborane synthesis
S B Jennifer Kan1, Xiongyi Huang1, Yosephine Gumulya1
1Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Boulevard, MC 210-41, Pasadena, California 91125, USA.
Researchers engineered bacteria to create chiral organoboranes, a novel chemical bond not found in nature. This genetically encoded platform enables efficient, tunable biosynthesis of these compounds within living cells.
Area of Science:
- Biocatalysis and enzyme engineering
- Synthetic organic chemistry
- Metabolic engineering
Background:
- Enzyme engineering enables novel catalytic functions beyond natural capabilities.
- Cellular production of non-natural chemical bonds requires compatible enzymes and reagents.
- Creating chiral organoboranes in vivo presents significant synthetic challenges.
Purpose of the Study:
- To develop a genetically encoded bacterial platform for producing chiral organoboranes.
- To discover and evolve enzyme variants for efficient carbon-boron bond formation.
- To establish a tunable system for boron manipulation within living organisms.
Main Methods:
- Discovery of carbene insertion into boron-hydrogen bonds by wild-type Rhodothermus marinus cytochrome c (Rma cyt c) in Escherichia coli.
- Directed evolution of Rma cyt c to enhance activity and specificity for organoborane synthesis.
- Optimization of whole-cell biocatalysis for gram-scale production.
Main Results:
- A platform for producing 16 novel chiral organoboranes using engineered Rma cyt c in E. coli.
- High catalytic efficiency: up to 15,300 turnovers, 6,100 h⁻¹, 99:1 enantiomeric ratio, and 100% chemoselectivity.
- Engineered enzymes showed higher activity in whole-cell systems compared to purified forms.
- Tunable enantiopreference allowed production of either enantiomer.
Conclusions:
- Established a DNA-encoded, engineerable bacterial platform for borylation.
- Achieved catalytic turnovers over 400-fold greater than existing chiral catalysts.
- Demonstrated the potential to expand boron chemistry applications within living systems.
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