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.