A platform for efficiently producing aliphatic, aromatic, and heterocyclic primary diamines from alcohols

Abstract

Microbial production of a broad range of primary diamines remains challenging due to unknown biosynthetic pathways and the limited availability of promiscuous enzymes. In this study, we engineered a platform strain of Escherichia coli capable of efficiently producing aliphatic, aromatic, and heterocyclic primary diamines from readily available alcohols. A concise three-enzyme cascade was designed to enable the self-recycling of both the cofactor NADP⁺ and the amine donor L-Glu. Notably, rational engineering of the pathway enzymes improved catalytic activity toward substrates bearing both hydroxyl and amine groups. By optimising the expression levels of the enzymes, the platform achieved the highest reported conversion for 1,4-bis(aminomethyl)cyclohexane, with a titer of 22.8 g L⁻¹ and a conversion rate of 77.0%. At a substrate concentration of 50 mM, the strain also efficiently converted various alcohols to produce aliphatic (70.6%–90.3%), aromatic (12.0%–78.2%), and heterocyclic (7.3%–50.2%) primary diamines and monoamines. This work provides a practical and scalable foundation for the industrial production of biodegradable polymer precursors.