Merger of Whole Cell Biocatalysis with Organocatalysis Upgrades Alcohol Feedstocks in a Mild, Aqueous, One-Pot Process

Abstract

Biosynthetic methods have the potential to deliver value-added chemicals from renewable feedstocks. However, despite major advances in metabolic engineering and synthetic biology, the rapid engineering of microbes to deliver high yields and titers of target compounds remains as a challenge. Here, we disclose a new chemical catalysis-based strategy for expanding the types of products available from unmodified microorganisms. By combining Gluconobacter oxidans as a whole cell biocatalyst in a single pot with a lysine organocatalyst, we demonstrate that aqueous solutions of Cn n-aliphatic alcohols are converted to C2n α,β-unsaturated aldehydes in a single pot in mild conditions. This carbon-doubling reaction works with a range of C2–C6 alcohol substrates. In the absence of the lysine organocatalyst, only n-aliphatic carboxylic acids are observed, indicating that the organocatalyst intercepts metabolic intermediates and redirects flux toward target chemicals. Taken together, our work reveals a new strategy of flux redirection to expand the scope of products from biosynthetic processes.

Biocatalytic Oxidation of Alcohols

“…Starting e.g., from 1-butanol, 2-ethyl hexenal can be obtained representing an interesting approach to upgrade bio-based alcohols. Finally, a recently established combination of biocatalytic (ADH-or AlcOx-catalyzed) alcohol oxidation with organocatalytic (amino acid-catalyzed) aldol condensation is worth mentioning (Scheme 14) [129][130][131]. Starting e.g., from 1-butanol, 2-ethyl hexenal can be obtained representing an interesting approach to upgrade bio-based alcohols.…”

Interfacing non-enzymatic catalysis with living microorganisms

“…In a subsequent study, Stewart and co-workers showed that the aldehyde substrate could be produced via the oxidation of primary alcohols by wild-type Gluconobacter oxydans . 41 Coupling this with a lysine organocatalyst at 900 mol% provided the target α,β-unsaturated products in up to 88% yield over 24–48 h, redirecting metabolism away from further oxidation of the aldehyde to the carboxylic acid by native dehydrogenases. A range of cross-aldol products could also be obtained through addition of other C 2 –C 6 alcohol substrates ( Fig.…”

Enhancing Biosynthesis and Manipulating Flux in Whole Cells with Abiotic Catalysis

“…We recently expanded this system to show that organocatalysts can intercept microbial metabolites and redirect flux to industrially relevant compounds without the need to engineer the microorganism (Figure 8). [81] Aqueous solutions of n‐aliphatic alcohols were oxidized to their corresponding n‐aliphatic aldehydes with Gluconobacter oxydans whole cell biocatalysis. In the absence of lysine, which acts as an aldol catalyst, the aldehyde is further oxidized to the corresponding carboxylic acid.…”