Fatty acids microbial hydroxylation

Another process patented by Givaudan uses Mucor circinelloides as a biocatalyst for the production of 4-decanolide [228]. Here the natural substrate is the ethyl ester of decanoic acid which is isolated from coconut oil. The key microbial activity harnessed in this process is the stereoselective and regioselective hydroxylation of the fatty acid in the y-position, which is followed by spontaneous lactonisation of the hydroxy fatty acid under acidic conditions and results in yields of up to 10.5 g 4-decanolide after 60 h. 

Epoxidation of various olefins by cytochrome P-450 enzymes has been studied using rat liver microsomes [29,30] as well as using enzymes from microbial origin. For example, Ruettinger and Fulco [31] reported the epoxidation of fatty acids such as palmitoleic acid by a cytochrome P-450 from Bacillus megaterium. Their results indicate that both the epoxidation and the hydroxylation processes are catalyzed by the same NADPH-dependent monooxygenase. More recently, other researchers demonstrated that the cytochrome P-450cam from Pseudomonas putida, which is known to hydroxylate camphor at a non-activated carbon atom, is also responsible for stereoselective epoxidation of cis- -methylstyrene [32]. The (lS,2R)-epoxide enantiomer obtained showed an enantiomeric purity (ee) of 78%. This result fits the predictions based on a theoretical approach (Fig. 2). 

Kim KR, Oh DK (2013) Production of hydroxy fatty acids by microbial fatty acid-hydroxylation enzymes. Biotechnol Adv 31 1473-1485... 

Very recently, lactones have received increasing attention as potential renewable platform chemicals. Perhaps the most prominent bio-based hydroxy fatty acids lactic acid, whose cyclic ester of two lactate molecules serves precursor for the synthesis of bio-based polymers. Fermentative production of hydroxyl-carboxylic acids from agro-industrial waste is an alternative to the synthesis from dwindling fossil resources (Fiichtenbusch et al. 2000). The enzymatic machinery for the production of polyhydroxyalkanoates (PHA) in bacteria offers catalytic pathways for the production of these lactone precursors (Efe et al. 2008). Recent examples include the microbial synthesis of y-butyrolactone and y-valerolactone. Particularly y-valerolactone is of importance and ranks among the top key components of the biomass-based economy. Microbial processes thus offer the perspective of a sustainable fermentative production of optically pure renewable lactones. 

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