α-Methylenation of metabolic aldehydes via a biocompatible aldol condensation Jonathan Dennis 2 and Stephen Wallace 1 1 IQB3, University of Edinburgh, UK and 2 University of Edinburgh, UK Biocompatible chemistry enables the interfacing of non-enzymatic catalysis with engineered microbial metabolism 1–3 . Although various aldehydes can be produced by Escherichia coli , aldehyde derivatisation in living systems is unexplored. Here we show that butanal produced from glucose by engineered E. coli undergoes α-methylenation in the presence of formaldehyde and various biocompatible organocatalysts. There is no known enzyme capable of aldehyde α-methylenation, and there are few examples of catalytic routes. Intriguingly, E. coli cells catalyse in situ C=C reduction of the methylenation product 2-methylenebutanal to form 2-methylbutanal. This formal α-methylation has no known enzymatic equivalent. Our results demonstrate that a metabolic pathway can be interfaced with biocompatible organocatalysis. Further metabolic engineering to produce other aldehydes could enable formal α-alkylation, a transformation that remains elusive in green chemistry.
Figure 1. Interfacing aldehyde biosynthesis with biocompatible organocatalysts in living E. coli References 1. S. Wallace and E. P. Balskus, Curr. Opin. Biotechnol. , 2014, 30 , 1–8.S. Wallace, E. E. Schultz and E. P. Balskus, Curr. Opin. Chem. Biol. , 2015, 25 , 71–79. 2. J. C. Sadler, J. A. Dennis, N. W. Johnson and S. Wallace, RSC Chem. Biol. , 2021, 2 , 1073–1083.
P13
© The Author(s), 2022
Made with FlippingBook Learn more on our blog