Abstract
Monocyclic phenols and catechols are important antioxidant compounds for the food and pharmaceutic industries; their production through biotransformation of low-added value starting compounds is of major biotechnological interest. The toluene o-xylene monooxygenase (ToMO) from Pseudomonas sp. OX1 is a bacterial multicomponent monooxygenase (BMM) that is able to hydroxylate a wide array of aromatic compounds and has already proven to be a versatile biochemical tool to produce mono- and dihydroxylated derivatives of aromatic compounds. The molecular determinants of its regioselectivity and substrate specificity have been thoroughly investigated, and a computational strategy has been developed which allows designing mutants able to hydroxylate non-natural substrates of this enzyme to obtain high-added value compounds of commercial interest. In this work, we have investigated the use of recombinant ToMO, expressed in cells of Escherichia coli strain JM109, for the biotransformation of non-natural substrates of this enzyme such as 2-phenoxyethanol, phthalan and 2-indanol to produce six hydroxylated derivatives. The hydroxylated products obtained were identified, isolated and their antioxidant potential was assessed both in vitro, using the DPPH assay, and on the rat cardiomyoblast cell line H9c2. Incubation of H9c2 cells with the hydroxylated compounds obtained from ToMO-catalyzed biotransformation induced a differential protective effect towards a mild oxidative stress induced by the presence of sodium arsenite. The results obtained confirm once again the versatility of the ToMO system for oxyfunctionalization reactions of biotechnological importance. Moreover, the hydroxylated derivatives obtained possess an interesting antioxidant potential that encourages the use of the enzyme for further functionalization reactions and their possible use as scaffolds to design novel bioactive molecules.
Highlights
In living organisms, aerobic metabolic processes such as respiration and photosynthesis cause the generation of reactive species of either oxygen (ROS) or nitrogen (RNS) in specific organelles such as mitochondria, chloroplasts, and peroxisomes
The different studies presented on the toluene o-xylene monooxygenase (ToMO) multicomponent system in more than a decade [18,20,21,23,24,25,26,27,28,29,30,31] described the unique versatility of the catalytic activity of this enzyme, which allows to obtain hydroxylated derivatives from a wide array of aromatic substrates, highlighting its role as a potential resource for the biosynthesis of phenolic and catecholic compounds
We have previously shown that a fine-tuning of the regioselectivity and of the catalytic efficiency of ToMO on 2-phenylethanol, a non-natural substrate, to produce known antioxidants such as tyrosol and hydroxytyrosol could be achieved by using an optimized computational model that allows a careful alteration of the shape of the active site [26,18]
Summary
Aerobic metabolic processes such as respiration and photosynthesis cause the generation of reactive species of either oxygen (ROS) or nitrogen (RNS) in specific organelles such as mitochondria, chloroplasts, and peroxisomes. Both ROS and RNS share a welldocumented role in stimulating physiological events such as signaling and cell differentiation. The quest for novel natural and synthetic antioxidants has undoubtedly drawn the attention of the scientific community in recent years In this context, several antioxidant pharmacophores have been identified, among which phenols and catechols have been given much attention as they are very susceptible to oxidation by acting as electron donors [6, 7]
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