Engineered fatty acid catabolism for fuel and chemical production

Abstract

Fatty acid oxidation pathways are attractive for metabolic engineering purposes due to their cyclic nature as well as their reactions that allow for the selective functionalization of alkyl chains. These characteristics allow for the production of various chemicals, such as alcohols, alkanes, ketones and hydroxyacids, in a wide range of carbon numbers. To this end, the α-, β-, and ω-oxidation pathways have been engineered for use in various hosts. Furthermore, the β-oxidation pathway has been engineered to operate in reverse, resulting in a promising carbon chain elongation platform. This review will describe the recent progress in metabolic engineering strategies for the production of chemicals through these fatty acid oxidation pathways.

Biocatalytic Oxidative Cascade for the Conversion of Fatty Acids into α‐Ketoacids via Internal H2O2 Recycling

“…The functionalization of fatty acids to α‐ketoacids is attractive from a synthetic standpoint as follow‐up chemistry can grant access to a multitude of renewable‐based synthons: amino acids, aldehydes, amines, C1‐truncated (odd‐numbered) carboxylic acids, and even alkanes . To overcome the abovementioned shortcomings of H 2 O 2 ‐mediated enzymatic oxidation protocols, we envisioned a one‐pot two‐step enzymatic cascade for the conversion of saturated fatty acids to α‐ketoacids.…”

Designing and Creating a Synthetic Omega Oxidation Pathway in Saccharomyces cerevisiae Enables Production of Medium-Chain α, ω-Dicarboxylic Acids

“…The process from hydroxylation of terminal alkyl carbon (the carbon most distant from the carboxyl group of the fatty acid) of fatty acid to an alcohol, and then finally to a dicarboxylic acid is known as omega oxidation (ω-oxidation). Verkade and Van Der Lee (1934) first proposed ω-oxidation of fatty acids in vivo which almost occurs in fungi, higher plants and animals ( Miura, 2013 ; Kim et al, 2016 ). The critical process of ω-oxidation is catalyzed by a hemoprotein cytochrome P450 enzyme which generally convert fatty acids to hydroxyfatty acids ( Wanders et al, 2011 ).…”

“…The range of different chemical transformations performed by P450s is also substantial, and continues to expand through interrogation of the properties of novel P450s, and selective hydroxylation can be undertaken on a highly functionalized molecule without the need for functional group protection ( Lundemo and Woodley, 2015 ; Girvan and Munro, 2016 ). However, it is easy to find amounts of cytochrome P450s with function of fatty acid hydroxylation in nature, but high active cytochrome P450s for ω-oxidation of medium-chain fatty acids or hydrocarbons were not available ( Scheps et al, 2011 ; Kim et al, 2016 ). Hence, both rational design and directed evolution approaches were developed to obtain efficient cytochrome P450s with higher substrate selectivity ( Renault et al, 2007 ; Behrendorff et al, 2015 ).…”

An Ancient Chinese Herbal Decoction Containing Angelicae Sinensis Radix, Astragali Radix, Jujuba Fructus, and Zingiberis Rhizoma Recens Stimulates the Browning Conversion of White Adipocyte in Cultured 3T3-L1 Cells

“…The key function of fatty acid catabolism is to generate ATP, and thus fat oxidation is a key switch to reveal catabolism progress [11, 27]. CPT1A is recognized in precipitating mitochondrial activities and accelerating fatty acid oxidation [26].…”