Microbial Production of 4-Methylpentanol from Glucose

Technology

This technology describes a method of metabolic engineering for the microbial production of branched, medium chain alcohols. The proposed metabolic pathway is composed of enzymes from multiple organisms and pathways, recombinantly expressed in E. coli. In one iteration of the process, two precursors (isobutyryl-CoA and acetyl-CoA) are generated from glycolysis, condensed to form a branched intermediate, and reduced to the final product, 4MP, in six steps. The pathway can be modulated based on enzyme expression to produce a variety of branched, medium chain alcohols.   

Problem Addressed

Economic and environmental concerns about petrochemical usage have led to increased interest in biofuels. Alcohols with medium to long carbon chains (C5 or greater) are attractive biofuels with a high energy density, but are not naturally produced in microorganisms. Previous metabolic engineering efforts have generally produced an insufficient yield for commercial purposes, especially due to large amounts of related byproducts. As yet, no large-scale production of 4MP in particular has been achieved. The novel synthesis route described within is capable of producing 4MP with high selectivity for industrial synthesis, and can be altered to synthesize a variety of branched, medium chain alcohols.  

Advantages      

• Highly selective biosynthetic route to 4MP for large-scale production
• Utilizes glucose as an inexpensive carbon sourceBranched, medium chain alcohols (e.g., 4MP) have a high energy density and improved octane rating
• Branched, medium chain alcohols (e.g., 4MP) exhibit low water solubility, allowing for relatively easy post-production purification   

Publications

"Retro-Biosynthetic Screening of a Modular Pathway Design Achieves Selective Route for Microbial Synthesis of 4-Methyl-Pentanol." Nature Communications, September 24, 2014.