Journal Menu► ▼ Journal Menu
Journal Browser► ▼ Journal Browser
Special Issue "Flavin Monooxygenases"
Deadline for manuscript submissions: 31 December 2019.
The selective oxidation of organic molecules is not only fundamentally important for life but also very useful for industrial applications. These oxidations can be carried out in many different ways, but in the era of “green chemistry”—more environmentally friendly reactions utilising less toxic reagents and ambient temperatures—enzymatic oxyfunctionalisation is deemed the most effective and suitable strategy. In this respect, one popular group of enzymes currently under investigation are flavin-dependent monooxygenases, and in particular single-component enzymes of class B, including flavin-containing monooxygenases (FMOs) and Baeyer–Villiger monooxygenases (BVMOs). The reason behind their popularity is the vast array of reactions that they can catalyse, including Baeyer–Villiger oxidation, sulfoxidation, epoxidation and N-oxidations. In addition, they are highly selective in their chemo-, regio-, and enantio-selective oxygenation reactions, and find wide applications in various fields, including high-value fine chemicals, cosmetics, as well as drug metabolites in the pharmaceutical industries. In the case of human FMOs, an important role is also played in drug metabolism.
The present Special Issue therefore aims to cover recent progress in not only possible new applications of these enzymes as biocatalysts, but also their emerging roles in human health and disease.
Prof. Sheila Sadeghi
Prof. Gianfranco Gilardi
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Catalysts is an international peer-reviewed open access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- Protein engineering
- Drug metabolites
- Fine chemicals
- Human disease
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Trimethylamine-N-Oxide: conserving it or eliminating it? Multiple perspectives across biological origins and functions
Gianluca Catucci, Sheila Sadeghi, Gianfranco Gilardi, Giulia Querio, Renzo Levi
Dept. Life Sciences and Systems Biology, University of Turin, Italy
Abstract: Trimethylamine N-Oxide (TMAO) is the product of the monooxygenase reaction catalyzed by a drug metabolizing enzyme: human flavin-containing monooxygenase 3 and its animal orthologues. For several years researchers have looked at TMAO or hFMO3 as two distinct molecules playing specific roles, the former to defend salt water animals from osmotic or hydrostatic stress and the latter to process xenobiotics in men. The presence of high levels of plasmatic trimethylamine-N-oxide (TMAO) in elasmobranchs and other animals was demonstrated a long time ago, whereas the actual physiological role of human flavin-containing monooxygenase 3 (hFMO3) is still unknown because the enzyme was mainly characterized for its ability to oxidize drugs. Recently TMAO was found to be related to several relevant health issues such as atherosclerosis, cardiovascular and renal diseases. This correlation poses a striking question of how other vertebrates (and invertebrates) can survive in the presence of very high TMAO concentrations (micromolar in humans, millimolar in marine mammals and several hundred millimolar in elasmobranchs).
It becomes therefore important to address how TMAO, its precursors and FMO catalytic activity are interconnected. In this network bacteria in food and gut have a crucial processing role.
Insights into the mechanism of ethionamide resistance in Mycobacterium tuberculosis through an in silico structural evaluation of EthA and mutants identified in clinical isolates
Priscila Caprilesa*, Deborah Antunesb*, Ernesto Caffarenab, Lucas Machadoc, Ana Carolina Ramos Guimarãesc#, Teca GalvãocAbstract: Ethionamide is used to treat patients with a complex record of tuberculosis treatment, usually caused by Mycobacterium tuberculosis isolates that are at least multidrug resistant. Ethionamide is a pro-drug activated by EthA, a flavin adenine dinucleotide (FAD) containing Baeyer-Villiger monooxygenase (BVMO). EthA mutation is the most frequent cause of ethionamide resistance; however, the mechanisms through which resistance occurs remain mostly uncharacterised. In previous work, we identified a region of EthA that concentrates mutations in ethionamide resistant Mycobacterium tuberculosis clinical isolates. Mutations in only three positions (E36, T44 and Y50) represent nearly 10% of all non synonymous mutations found in EthA in over 160 resistant isolates described in the literature. These amino acids are in a conserved region of 29 residues that contains six of eleven active site residues of the Pseudomonas putida enzyme 2-oxo-Δ3-4,5,5-trimethylcyclopentenylacetyl-CoA monooxygenase, OTEMO. In the OTEMO structure, the equivalent amino acids to those found mutated in EthA contact or are very close to the FAD molecule. In the study proposed we will use computational approaches such as comparative modelling, molecular docking and molecular dynamics to evaluate the impact of the mutations at these three positions on protein structure as well as on the interaction with FAD and ethionamide.