Bacterial L-amino acid oxidase (LAAO) is believed to play important biological and ecological roles in marine niches, thus attracting increasing attention to understand the regulation mechanisms underlying its production. In this study, we investigated genes involved in LAAO production in marine bacterium Pseudoalteromonas sp. Rf-1 using transposon mutagenesis. Of more than 4,000 mutants screened, 15 mutants showed significant changes in LAAO activity. Desired transposon insertion was confirmed in 12 mutants, in which disrupted genes and corresponding functionswere identified. Analysis of LAAO activity and lao gene expression revealed that GntR family transcriptional regulator, methylase, non-ribosomal peptide synthetase, TonB-dependent heme-receptor family, Na+/H+ antiporter and related arsenite permease, N-acetyltransferase GCN5, Ketol-acid reductoisomerase and SAM-dependent methytransferase, and their coding genes may be involved in either upregulation or downregulation pathway at transcriptional, posttranscriptional, translational and/or posttranslational level. The nhaD and sdmT genes were separately complemented into the corresponding mutants with abolished LAAO-activity. The complementation of either gene can restore LAAO activity and lao gene expression, demonstrating their regulatory role in LAAO biosynthesis. This study provides, for the first time, insights into the molecular mechanisms regulating LAAO production in Pseudoalteromonas sp. Rf-1, which is important to better understand biological and ecological roles of LAAO.
L-amino acid oxidase (LAAO) is widely distributed in many different organisms and found to play important biological roles, thus attracting a great deal of attention for characterization of its activity. Diverse detection methods with their own properties have been established. This review advanced different LAAO activity assays based on substrate consumption, cofactor amount, and product accumulation. The description of benefits and drawbacks of each method is expected to help researchers find appropriate detection method of LAAO activity for their own purpose.
Janus Kinase (JAK), a nonreceptor protein tyrosine kinase, has emerged as an excellent target through research and development since its discovery in the 1990s. As novel small-molecule targeted drugs, JAK inhibitor drugs have been successfully used in the treatment of rheumatoid arthritis (RA), myofibrosis (MF) and ulcerative colitis (UC). With the gradual development of JAK targets in the market, JAK inhibitors have also received very considerable feedback in the treatment of autoimmune diseases such as atopic dermatitis (AD), Crohn's disease (CD) and graft-versus host disease (GVHD). This article reviews the research progress of JAK inhibitor drugs: introducing the existing JAK inhibitors on the market and some JAK inhibitors in clinical trials currently. In addition, the synthesis of various types of JAK inhibitors were summarized, and the effects of different drug structures on drug inhibition and selectivity.
Here, we report a draft 5.58-Mb genome sequence of Pseudoalteromonas sp. strain R3, isolated from an intertidal-zone sludge sample, which has l-amino acid oxidase activity. The genomics information of this strain will facilitate the study of l-amino acid oxidase, quorum sensing, and the relationship of the two.
According to the 2017 ILAE's official definition, epilepsy is a slow brain disease state characterized by recurrent episodes. Due to information released by ILAE in 2017, it can be divided into four types, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and unknown epilepsy. Since 1989, 24 new antiepileptic drugs have been approved to treat different types of epilepsy. Besides, there are a variety of antiepileptic medications under clinical monitoring. These novel antiepileptic drugs have plenty of advantages. Over the past 33 years, there have been many antiepileptic drugs on the mearket, but no one has been found that can completely cure epilepsy. In this paper, the mentioned drugs were classified according to their targets, and the essential information, and clinical studies of each drug were described. The structure-activity relationship of different chemical structures was summarized. This paper provides help for the follow-up research on epilepsy drugs.
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