Tyramine Derivatives Catalyze the Aldol Dimerization of Butyraldehyde in the Presence of Escherichia coli

Abstract

Biogenic amine organocatalysts have transformed the field of synthetic organic chemistry. Yet despite their use in synthesis and to label biomolecules in vitro, amine organocatalysis in vivo has received comparatively little attention -despite the potential of such reactions to be interfaced with living cells and to modify cellular metabolites. Herein we report that biogenic amines derived from L-tyrosine catalyze the self-aldol condensation of butanal to 2-ethylhexenal -a key intermediate in the production of the bulk chemical 2-ethylhexanol -in the presence of living Escherichia coli and outperform many amine organocatalysts currently used in synthetic organic chemistry. Furthermore, we demonstrate that cell lysate from E. coli and the prolific amine overproducer Corynebacterium glutamicum ATCC 13032 catalyze this reaction in vitro, demonstrating the potential for microbial metabolism to be used as a source of organocatalysts for biocompatible reactions in cells.

One-pot cascade reactions for the synthesis of dinitroalkanes in aqueous buffer

“…18,19 Building off of this work, we sought to expand upon the products accessible through the merger of biocatalysis and organocatalysis. Previous efforts to combine organocatalysis and biocatalysis include the synthesis of optically active diols, 20 aminolactones, 21 indole derivatives, 22 and aldol condensation products, 23 among others. 24 Toward our goal of synthesizing dinitroalkanes under mild conditions, we envisioned using an enzyme or whole-cell biocatalyst to produce an aldehyde from an alcohol substrate.…”

Biocompatible α‐Methylenation of Metabolic Butyraldehyde in Living Bacteria

“…This is pertinent as synthetic biology approaches continue to produce compounds of industrial value, and because methods to diversify metabolites accessible via this approach are needed to replace petrochemical feedstocks [8–10] . To this end, we recently demonstrated the use of tyramine derivatives, and cellular amines from Corynebacterium glutamicum as biocompatible organocatalysts for the self‐aldol dimerisation of exogenous butyraldehyde in the presence of E. coli [11] . However, the use of biocompatible organocatalysis with engineered metabolic pathways in a living cell remains an outstanding challenge [9,12] .…”

“…To our knowledge, no enzyme is known to catalyse the α‐methylenation or α‐methylation of aldehydes in Nature, and 2‐MB/2‐MBA have never been accessed via microbial fermentation. Furthermore, we have recently reported that E. coli possesses a series of putative reductases in its genome with homology to ene‐reductases from Gluconobacter oxydans that can catalyze the reduction of α,ß‐unsaturated aldehydes, meaning 2‐MB could potentially be further processed to 2‐MBA via endogenous enzymes when generated in vivo (Table S15) [11] . In addition, we were inspired by recent seminal work by Goodwin et al.…”

“…[8][9][10] To this end, we recently demonstrated the use of tyramine derivatives, and cellular amines from Corynebacterium glutamicum as biocompatible organocatalysts for the self-aldol dimerisation of exogenous butyraldehyde in the presence of E. coli. [11] However, the use of biocompatible organocatalysis with engineered metabolic pathways in a living cell remains an outstanding challenge. [9,12] Herein we report that Lproline derivatives and/or cellular phosphate catalyse the non-enzymatic biocompatible α-methylenation of butyraldehyde in living E. coli.…”

“…Furthermore, we have recently reported that E. coli possesses a series of putative reductases in its genome with homology to ene-reductases from Gluconobacter oxydans that can catalyze the reduction of α,ß-unsaturated aldehydes, meaning 2-MB could potentially be further processed to 2-MBA via endogenous enzymes when generated in vivo (Table S15). [11] In addition, we were inspired by recent seminal work by Goodwin et al demonstrating that exogenous α-and ß-amino acids mediate the self-aldol reaction of aldehydes generated from exogenous alcohols by alcohol oxidases or the bacterium G. oxydans. [14][15][16] However, the use of non-enzymatic organo-catalytic aldol chemistry with engineered metabolic pathways has yet to be achieved.…”