New frontiers in flavin-dependent monooxygenases

Reis, Renata A.G.; Li, Hao; Johnson, Maxim; Sobrado, Pablo

doi:10.1016/j.abb.2021.108765

Cited by 49 publications

(44 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The range of natural diversity of FMOs, to which Tet Xs belong, is extraordinary and includes a wide variety of enzymes involved in different oxygenation reactions [31]. These broad spectra are also reflected in the ability to destroy a range of antimicrobials, which presently include tetracyclines, rifampicins, sulfonamides, and β-lactams [32]. Besides tetracyclines, which are discussed here, these targets, for example, are represented by aromatic polyketides such as rifampicins [33][34][35].…”

Section: Diversity Of Fmo-encoding and Tet(x) Genesmentioning

confidence: 99%

“…Similarly, a recently identified class D FMO is capable of degrading sulphonamides, and the corresponding gene, sulX, is associated with MGEs [39]. Thus, due to their abundance in the environmental microbiota and broad substrate capacity, FMOs are capable of inactivating a number of antimicrobials of different classes via oxygenation reactions [32]. Although there are substantial structural differences between the older and newer generations of tetracyclines, a variety of FMO/Tet X enzymes are capable of degrading all of them [19,28].…”

Section: Diversity Of Fmo-encoding and Tet(x) Genesmentioning

confidence: 99%

“…Some genes in a new cellular environment thus could occasionally confer resistance to antimicrobials and then are selected as AMR genes. This scenario has been possibly instigated in the case of FMOs, some of which happened to have enzymatic activities capable of destructing certain antimicrobials including the next-generation tetracyclines [32]. This chain of events leading to the rise and dissemination of tet(X) is depicted in Figure 3.…”

Section: Emergence and Rise Of Amr: From Chromosomal Mutations To Acquired Mobile Resistancementioning

confidence: 99%

See 2 more Smart Citations

Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study

Aminov

2021

IJMS

View full text Add to dashboard Cite

Understanding the mechanisms leading to the rise and dissemination of antimicrobial resistance (AMR) is crucially important for the preservation of power of antimicrobials and controlling infectious diseases. Measures to monitor and detect AMR, however, have been significantly delayed and introduced much later after the beginning of industrial production and consumption of antimicrobials. However, monitoring and detection of AMR is largely focused on bacterial pathogens, thus missing multiple key events which take place before the emergence and spread of AMR among the pathogens. In this regard, careful analysis of AMR development towards recently introduced antimicrobials may serve as a valuable example for the better understanding of mechanisms driving AMR evolution. Here, the example of evolution of tet(X), which confers resistance to the next-generation tetracyclines, is summarised and discussed. Initial mechanisms of resistance to these antimicrobials among pathogens were mostly via chromosomal mutations leading to the overexpression of efflux pumps. High-level resistance was achieved only after the acquisition of flavin-dependent monooxygenase-encoding genes from the environmental microbiota. These genes confer resistance to all tetracyclines, including the next-generation tetracyclines, and thus were termed tet(X). ISCR2 and IS26, as well as a variety of conjugative and mobilizable plasmids of different incompatibility groups, played an essential role in the acquisition of tet(X) genes from natural reservoirs and in further dissemination among bacterial commensals and pathogens. This process, which took place within the last decade, demonstrates how rapidly AMR evolution may progress, taking away some drugs of last resort from our arsenal.

show abstract

Section: Diversity Of Fmo-encoding and Tet(x) Genesmentioning

confidence: 99%

Section: Diversity Of Fmo-encoding and Tet(x) Genesmentioning

confidence: 99%

Section: Emergence and Rise Of Amr: From Chromosomal Mutations To Acquired Mobile Resistancementioning

confidence: 99%

See 1 more Smart Citation

Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study

Aminov

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…tetracycline, sulfonamides, rifampicin and imipenem (Kim, Thawng, Lee, Wellington, & Cha, 2019;Koteva et al, 2018;Minerdi et al, 2016). In general, it uses NADH or NADPH as an electron donor to catalyze various reactions such as hydroxylation of the substrate, Baeyer-Villiger oxidation and halogenation of the epoxidation, etc (Ceccoli, Bianchi, & Rial, 2014;Mascotti, Juri Ayub, Furnham, Thornton, & Laskowski, 2016;Reis, Li, Johnson, & Sobrado, 2021). In light of the sequence and biochemical characteristics, FMOs are divided into eight categories A-H.…”

Section: Action Of Tet(x)mentioning

confidence: 99%

Transferability of tigecycline resistance: Characterization of the expanding Tet(X) family

Cui

Chen

Qian

et al. 2021

WIREs Mechanisms of Disease

View full text Add to dashboard Cite

Tetracycline and its derivative tigecycline are clinical options against Gramnegative bacterial infections. The emergence of mobile Tet(X) enzymes that destruct tetracycline-type antibiotics is posing a big challenge to antibacterial therapy and food/environmental securities. Here, we present an update on a growing number of Tet(X) variants. We describe structure and action of Tet(X) enzyme, and discuss the evolutional origin. In addition, potential Tet(X) inhibitors are given. This mini-review might benefit better understanding of Tet(X)mediated tigecycline resistance.

show abstract

“…Apart from these ligninolytic enzymes, aromatic compound-degrading, detoxifying enzymes, and highly reactive free radicals such as hydrogen peroxide, hydroxy radicals, superoxide, and reactive singlet oxygen ions also play a crucial role in the degradation of lignocellulosic units, in which superoxide dismutase (SOD), heme-peroxidases, dye-decolorizing peroxidase, alcohol dehydrogenase, iron reductase, ferredoxin, catalase, oxidoreductase, and another large set of enzymes involved in Flavin-containing Monooxygenases (FMOs) and Cytochrome P450s (CYPs) families were found in the SP02 genome. FMOs are importantly recognized when applied in the metabolism of nitrogen-, sulfur-, and other nucleophilic heteroatom-containing xenobiotics [73,74]. CYPs play diverse and critical roles in metabolism and fungal adaptation to specific ecological niches [75], are involved in the breakdown of various xenobiotics and lignin metabolites released by the action of extracellular peroxidases [76,77], and assist in stereo-and regio-specific oxidation of substrates [78].…”

Section: Gene Function Of C Unicolor Sp02mentioning

confidence: 99%

Genomic Studies of White-Rot Fungus Cerrena unicolor SP02 Provide Insights into Food Safety Value-Added Utilization of Non-Food Lignocellulosic Biomass

Zhang

Shah

Mohamed

et al. 2021

JoF

View full text Add to dashboard Cite

Cerrena unicolor is an ecologically and biotechnologically important wood-degrading basidiomycete with high lignocellulose degrading ability. Biological and genetic investigations are limited in the Cerrena genus and, thus, hinder genetic modification and commercial use. The aim of the present study was to provide a global understanding through genomic and experimental research about lignocellulosic biomass utilization by Cerrena unicolor. In this study, we reported the genome sequence of C. unicolor SP02 by using the Illumina and PacBio 20 platforms to obtain trustworthy assembly and annotation. This is the combinational 2nd and 3rd genome sequencing and assembly of C. unicolor species. The generated genome was 42.79 Mb in size with an N50 contig size of 2.48 Mb, a G + C content of 47.43%, and encoding of 12,277 predicted genes. The genes encoding various lignocellulolytic enzymes including laccase, lignin peroxidase, manganese peroxidase, cytochromes P450, cellulase, xylanase, α-amylase, and pectinase involved in the degradation of lignin, cellulose, xylan, starch, pectin, and chitin that showed the C. unicolor SP02 potentially have a wide range of applications in lignocellulosic biomass conversion. Genome-scale metabolic analysis opened up a valuable resource for a better understanding of carbohydrate-active enzymes (CAZymes) and oxidoreductases that provide insights into the genetic basis and molecular mechanisms for lignocellulosic degradation. The C. unicolor SP02 model can be used for the development of efficient microbial cell factories in lignocellulosic industries. The understanding of the genetic material of C. unicolor SP02 coding for the lignocellulolytic enzymes will significantly benefit us in genetic manipulation, site-directed mutagenesis, and industrial biotechnology.

show abstract

New frontiers in flavin-dependent monooxygenases

Cited by 49 publications

References 106 publications

Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study

Acquisition and Spread of Antimicrobial Resistance: A tet(X) Case Study

Transferability of tigecycline resistance: Characterization of the expanding Tet(X) family

Genomic Studies of White-Rot Fungus Cerrena unicolor SP02 Provide Insights into Food Safety Value-Added Utilization of Non-Food Lignocellulosic Biomass

Contact Info

Product

Resources

About