Conversion of alcohols to enantiopure amines through dual-enzyme hydrogen-borrowing cascades

• Published in: Science (American Association for the Advancement of Science) Vol. 349; no. 6255; pp. 1525 - 1529
• Main Authors: Mutti, Francesco G., Knaus, Tanja, Scrutton, Nigel S., Breuer, Michael, Turner, Nicholas J.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 25.09.2015; The American Association for the Advancement of Science
• Subjects: Alcohol; Alcohol Dehydrogenase - chemistry; Alcohol Dehydrogenase - genetics; Alcohols; Alcohols - chemistry; Amination; Amines; Amines - chemical synthesis; Bacillus; Bacillus - enzymology; Bacillus - genetics; Biocatalysis; Bioengineering; Biophysics; Byproducts; Cascades; Chemical engineering; Conversion; Enzymes; Genetic Engineering; Hydrogen - chemistry; Lactobacillus - enzymology; Lactobacillus - genetics; Organic Chemistry; Oxidoreductases Acting on CH-NH Group Donors - chemistry; Oxidoreductases Acting on CH-NH Group Donors - genetics; Synthesis (chemistry); Water
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aac9283

α-Chiral amines are key intermediates for the synthesis of a plethora of chemical compounds at industrial scale. We present a biocatalytic hydrogen-borrowing amination of primary and secondary alcohols that allows for the efficient and environmentally benign production of enantiopure amines. The method relies on a combination of two enzymes: an alcohol dehydrogenase (from Aromatoleum sp., Lactobacillus sp., or Bacillus sp.) operating in tandem with an amine dehydrogenase (engineered from Bacillus sp.) to aminate a structurally diverse range of aromatic and aliphatic alcohols, yielding up to 96% conversion and 99% enantiomeric excess. Primary alcohols were aminated with high conversion (up to 99%). This redox self-sufficient cascade possesses high atom efficiency, sourcing nitrogen from ammonium and generating water as the sole by-product.