Biocatalytic, one-pot diterminal oxidation and esterification of n-alkanes for production of α,ω-diol and α,ω-dicarboxylic acid esters

Metab Eng. 2017 Nov;44:134-142. doi: 10.1016/j.ymben.2017.10.005. Epub 2017 Oct 7.


Direct and selective terminal oxidation of medium-chain n-alkanes is a major challenge in chemistry. Efforts to achieve this have so far resulted in low specificity and overoxidized products. Biocatalytic oxidation of medium-chain n-alkanes - with for example the alkane monooxygenase AlkB from P. putida GPo1- on the other hand is highly selective. However, it also results in overoxidation. Moreover, diterminal oxidation of medium-chain n-alkanes is inefficient. Hence, α,ω-bifunctional monomers are mostly produced from olefins using energy intensive, multi-step processes. By combining biocatalytic oxidation with esterification we drastically increased diterminal oxidation upto 92mol% and reduced overoxidation to 3% for n-hexane. This methodology allowed us to convert medium-chain n-alkanes into α,ω-diacetoxyalkanes and esterified α,ω-dicarboxylic acids. We achieved this in a one-pot reaction with resting-cell suspensions of genetically engineered Escherichia coli. The combination of terminal oxidation and esterification constitutes a versatile toolbox to produce α,ω-bifunctional monomers from n-alkanes.

Keywords: Alkanes; Monooxygenases; Whole-cell biocatalysis; α,ω-dicarboxylic acids; α,ω-diols.

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Dicarboxylic Acids / metabolism*
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Esterification
  • Microorganisms, Genetically-Modified* / genetics
  • Microorganisms, Genetically-Modified* / metabolism
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism
  • Oxidation-Reduction
  • Pseudomonas putida / enzymology
  • Pseudomonas putida / genetics


  • Bacterial Proteins
  • Dicarboxylic Acids
  • Mixed Function Oxygenases