Biotransformations Utilizing β-Oxidation Cycle Reactions in the Synthesis of Natural Compounds and Medicines

Abstract

β-Oxidation cycle reactions, which are key stages in the metabolism of fatty acids in eucaryotic cells and in processes with a significant role in the degradation of acids used by microbes as a carbon source, have also found application in biotransformations. One of the major advantages of biotransformations based on the β-oxidation cycle is the possibility to transform a substrate in a series of reactions catalyzed by a number of enzymes. It allows the use of sterols as a substrate base in the production of natural steroid compounds and their analogues. This route also leads to biologically active compounds of therapeutic significance. Transformations of natural substrates via β-oxidation are the core part of the synthetic routes of natural flavors used as food additives. Stereoselectivity of the enzymes catalyzing the stages of dehydrogenation and addition of a water molecule to the double bond also finds application in the synthesis of chiral biologically active compounds, including medicines. Recent advances in genetic, metabolic engineering, methods for the enhancement of bioprocess productivity and the selectivity of target reactions are also described.

Characterization of p -Hydroxycinnamate Catabolism in a Soil Actinobacterium

“…Both pathways involve the initial activation of the acid by coenzyme A (CoASH) in a reaction catalyzed by an aryl-CoA synthetase, and both transform ferulate to vanillate and acetyl-CoA (11,12,13,14,15). The more commonly described of the two pathways has been experimentally verified.…”

“…In this pathway, feruloyl-CoA is transformed by a hydratase and a dehydrogenase to yield a ␤-ketoacyl-CoA. It has been proposed that this is cleaved by a ␤-ketothiolase to acetyl-CoA and vanillyl-CoA and that the latter is hydrolyzed by an acyl-CoA thioesterase (15). The last two steps have not been experimentally verified.…”

“…The vanillin is then oxidized to vanillate by a dehydrogenase (see Fig. S1 in the supplemental material) (1,15). A second pathway involving ␤-oxidation has been proposed to occur in Rhodotorula rubra, Rhodococcus sp.…”

Yarrowia lipolytica as an Oleaginous Cell Factory Platform for Production of Fatty Acid-Based Biofuel and Bioproducts

“…In fact, γ-decalactone can reach the production level of 10 g/L. Ricinoleic acid is converted to 4-hydroxydecanoic acid through four cycles of β-oxidation, and then undergoes lactonization under acidic conditions (Swizdor et al, 2012). However, it is not clear whether lactonization occurs on acyl-CoA or on the FFAs.…”

“…They can be the products of partial β-oxidation cycle through the reduction of β-ketoacids, oxidation of 1,3-diol, and subsequently, hydration of α,β-unsaturated acids (Swizdor et al, 2012). When using β-oxidation, further metabolization of β-hydroxy acids to the corresponding acids should be avoided by genetic engineering to increase molar conversion yield.…”