Fatty acid oxidation: systems analysis and applications

Fatty acids (FAs) are essential components of cellular structure and energy-generating routes in living organisms. They exist in a variety of chemical configurations and functionalities and are catabolized by different oxidative routes, according to their structure. α- and ω-Oxidation are minor routes that occur only in eukaryotes, while β-oxidation is the major degradation route in eukaroytes and prokaryotes. These pathways have been characterized and engineered from different perspectives for industrial and biomedical applications. The severity of FA oxidation disorders in humans initially guided the study of FA metabolism at a molecular-level. On the other hand, recent advances in metabolic engineering and systems biology have powered the study of FA biosynthetic and catabolic routes in microorganisms at a systems-level. Several studies have proposed these pathways as platforms for the production of fuels and chemicals from biorenewable sources. The lower complexity of microbial systems has allowed a more comprehensive study of FA metabolism and has opened opportunities for a wider range of applications. Still, there is a need for techniques that facilitate the translation of high-throughput data from microorganisms to more complex eukaryotic systems in order to aid the development of diagnostic and treatment strategies for FA oxidation disorders. In addition, further systems biology analyses on human systems could also provide valuable insights on oxidation disorders. This article presents a comparison of the three main FA oxidative routes, systems biology analyses that have been used to study FA metabolism, and engineering efforts performed on microbial systems.