Transforming inert cycloalkanes into α,ω-diamines through designed enzymatic cascade catalysis

Abstract Aliphatic α,ω-diamines (DAs) are important monomer precursors in polyamide plastic manufacturing. However, the dominant industrial process for DA synthesis involves energy-intensive, multistage chemical reactions that are harmful to the environment. For instance, 1,6-hexanediamine (HMD), one of most prominent monomers in nylon-66 synthesis, is mainly synthesized with currently high technological control by butadiene hydrocyanation, which suffers from the use of highly toxic hydrogen cyanide, unsatisfactory selectivity and a complex separation process. Thus, the development of sustainable green DA synthetic routes is highly desired. Herein, we report an efficient one-pot in vivo biocatalytic cascade for the transformation of cycloalkanes into DAs with the aid of advanced techniques, including the RetroBioCat tool for biocatalytic route design, enzyme mining for finding appropriate enzymes and microbial consortia construction for efficient pathway assembly. As a result, DAs are successfully produced by the developed microbial consortia-based biocatalytic system, especially HMD, and product concentrations as high as 16.5 mM and 7.6 mM are achieved when using cyclohexanol (CHOL) or cyclohexane (CH) as substrates, respectively. This also represents the highest HMD biosynthesis productivity to date. Other cycloalkanes also serve as substrates, indicating the generality of our approach.