Directed Synthesis of Biobased 1,6-Diaminohexane from Adipic Acid by Rational Regulation of a Functional Enzyme Cascade in Escherichia coli

Some enzymes are relatively specific when catalyzing substrates with similar chemical bonds, allowing a single enzyme to participate in multiple reactions. Such relative specificity brings great challenges to the synthesis of target products, especially in a whole-cell system. In this study, a redirected carboxylic acid reductase cascade was constructed in Escherichia coli for biosynthesis of the engineering plastics monomer 1,6-diaminohexane. A series of strategies were adopted to direct the biosynthesis of 1,6-diaminohexane, including mining of enzyme components, design of a cascade module, adaptation analysis and evaluation, and regulation of coenzyme elements, without any directed mutation of enzymes to change their specificity. The titer of 1,6-diaminohexane was increased 567-fold relative to the initial strain to 238.5 mg·L–1. The artificial pathway was proven to be universal for medium-chain diamines, showing the power of adaptive assembly of key elements to redirect flux for target production.