Microbial Production of Branched, Medium Chain Alcohol 4-Methyl-1-Pentanol from Glucose

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Microbial production of branched, medium chain alcohol 4-methyl-1-pentanol from glucose
Professor Kristala Prather
Department of Chemical Engineering, MIT
External Link (web.mit.edu)
Micah Sheppard
Department of Chemical Engineering, MIT
External Link (web.mit.edu)
Aditya Kunjapur
Department of Chemical Engineering, MIT
External Link (web.mit.edu)
Managed By
Michelle Hunt
MIT Technology Licensing Officer
Patent Protection

Microbial production of branched medium chain alcohols, such as 4-methylpentanol

US Patent Pending 2015-0132816
Retro-biosynthetic screening of a modular pathway design achieves selective route for microbial synthesis of 4-methyl-pentanol
Nature Communications, DOI: 10.1038/ncomms6031


Branched, medium chain alcohols are as energy dense as petroleum-derived gasoline and have a superior octane rating. As such, they provide an environmentally sustainable alternative to gasoline for use in spark ignition engines. 4-methyl-1-pentanol (4MP), in particular, can also be used as an organic solvent for a variety of reactions and extractions.  

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. As yet, no large-scale production of 4MP in particular has been achieved. The novel synthesis route described within is capable of producing large-scale yields of 4MP for industrial synthesis, and can be altered to synthesize a variety of branched, medium chain alcohols.


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. 


  • Increased pathway yield of 4MP for large-scale production
  • Utilizes glucose as an inexpensive carbon source
  • Branched, 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¬†