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

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 mediumchain 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 nalkanes is inefficient. Hence, alpha,omega-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 92 mol% and reduced overoxidation to 3% for n-hexane. This methodology allowed us to convert medium-chain n-alkanes into alpha,omega-diacetoxyalkanes and esterified alpha,omega-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 alpha,omega bifunctional monomers from n-alkanes.