Microbial Synthesis of Medium‐Chain α,ω‐Dicarboxylic Acids and ω‐Aminocarboxylic Acids from Renewable Long‐Chain Fatty Acids

Abstract

Biotransformation of long‐chain fatty acids into medium‐chain α,ω‐dicarboxylic acids or ω‐aminocarboxylic acids could be achieved with biocatalysts. This study presents the production of α,ω‐dicarboxylic acids (e.g., C9, C11, C12, C13) and ω‐aminocarboxylic acids (e.g., C11, C12, C13) directly from fatty acids (e.g., oleic acid, ricinoleic acid, lesquerolic acid) using recombinant Escherichia coli‐based biocatalysts. ω‐Hydroxycarboxylic acids, which were produced from oxidative cleavage of fatty acids via enzymatic reactions involving a fatty acid double bond hydratase, an alcohol dehydrogenase, a Baeyer–Villiger monooxygenase and an esterase, were then oxidized to α,ω‐dicarboxylic acids by alcohol dehydrogenase (ADH, AlkJ) from Pseudomonas putida GPo1 or converted into ω‐aminocarboxylic acids by a serial combination of ADH from P. putida GPo1 and an ω‐transaminase of Silicibacter pomeroyi. The double bonds present in the fatty acids such as ricinoleic acid and lesquerolic acid were reduced by E. coli‐native enzymes during the biotransformations. This study demonstrates that the industrially relevant building blocks (C9 to C13 saturated α,ω‐dicarboxylic acids and ω‐aminocarboxylic acids) can be produced from renewable fatty acids using biocatalysis.magnified image

Engineering and application of enzymes for lipid modification, an update

“…These oleate hydratases have in common, that they do not at all or only to a minor extent hydrate ∆12 double bonds in linoleic acid. Oh and coworkes, however, have identified a new ∆12-hydratase from Lactobacillus acidophilus, which predominantly forms the 13-hydroxy derivative of linoleic acid [133,134]. In addition, Hirata and coworkers showed that the ∆12-hydratase from Lactobacillus not only converts C18 cis PUFAs, but also arachidonic acid (C20) and DHA (C22) into the corresponding 15-hydroxy fatty acid and the14-hydroxy fatty acids, respectively [135].…”

“…What is more, the importance of regiospecific biocatalytic hydration as key step for the production of high-value-added products like flavors, resins, waxes, nylons, plastics, lubricants, polymers etc. from fatty acids can well be exemplified by multienzyme cascade reactions as described in three recent articles by Park and coworkers [134,138,139]. In these sequential enzymatic reactions, the hydration step of either oleic acid by a ∆9 hydratase [139] or linoleic acid by a novel ∆12 hydratase [138] forms the starting point for multi branched enzymatic cascades.…”

“…Next the sequence is split in an oxidation catalyzed by two different Baeyer-Villinger monooxygenase (BVMO) to access different regioisomeric esters: the BVMO from P. putida provides access to ω-hydroxyfatty acids whereas the BVMO from P. fluorescens leads to the formation of an α,ω-dicarboxylic acid ester after an esterase-catalyzed hydrolysis (Scheme 5). In a subsequent work, this sequence was extended further by employing both an alcohol hydrogenase to yield α,ϖ-dicarboxylic acids and a (S)-transaminase to gain access to ω-aminocarboxylic acids, which are industrially relevant building blocks [134]. When using linoleic acid instead of oleic acid as starting material, Oh et al [138] were also able to form lactones by adding whole-cell biotransformations with yeast to the sequence.…”

Production of medium-chain, a, omega-bifunctional monomers from fatty acids and n-alkanes

“…AlkJ was applied before to catalyse the conversion of alcohols to aldehydes in E. coli 78,113,117 . This is the first report of its functionality on 9-hydroxy ethyl nonanoate.…”

“…AlkJ has received attention since it can produce the terminal aldehydes that can be converted to amines by ω-transaminases 117,141 . In twoliquid phase conversions with AlkBGTJL, the aldehyde and alcohol intermediates still accumulated.…”