APPLIED AND ENVIRONMENTAL MICROBIOLOGY
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2017
·Vol. 83
·期 15
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IF 3.807
Erquan Chen,Qi Chen,Shaoming Chen,Bing Xu,Jianhua Ju,Huan Wang
Lantibiotics are antimicrobial peptides belonging to the family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and feature thioether linkages in their structures. In this study, we identified the biosynthetic gene cluster of a cinnamycin analog, named mathermycin, from Marinactinospora thermotolerans SCSIO 00652 and reconstituted its biosynthesis in Streptomyces lividans and Escherichia coli. Key posttranslational modification enzymes of mathermycin were characterized. Mathermycin exhibited antimicrobial activity and therefore represents an example of cinnamycin-like lantibiotics from Marinactinospora species.IMPORTANCE The discovery of new antimicrobial compounds that can be used as potential drugs is in urgent need due to increasing bacterial resistance to current antibiotics. Lantibiotics are important antimicrobial compounds that have found applications in both the clinic setting and food industry. We report here the discovery of a new lantibiotic, mathermycin, from a marine-derived Marinactinospora thermotolerans strain and elucidation of its biosynthesis. We also demonstrate that mathermycin possesses antimicrobial activity toward a Bacillus strain.
研究领域:
微生物学
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药物化学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2018
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IF 2.831
Li Zhu,Ruonan Liu,Tangrong Liu,Xuan Zou,Zhe Xu,Huashi Guan
Resistance to aminoglycoside antibiotics occurs primarily as a result of aminoglycoside-modification enzymes (AMEs) that modify the antibiotics. In this work, a novel strategy to combat the effects of antibiotic resistance was developed by screening multiple AMEs inhibitors with ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF MS). The method screened inhibitors of three AMEs (AAC(6’)-APH(2”), AAC(6’) and APH(2”)) simultaneously through measuring the acetyltransferase activity and phosphotransferase activity of AAC(6’)-APH(2”) enzyme in a single assay. Screening inhibitors of multiple targets could greatly improve the screening efficiency at early-stages of drug discovery. In this study, enzyme reaction conditions including cosubstrate, enzyme concentration and cosubstrate concentration were optimized. The inhibition constants ( K i ) for two known inhibitors, paromomycin and quercetin, were determined to be 1.23 and 20.27 μM, respectively. The assay was further validated through the determination of a high Z' factor value of 0.73. The developed assay was applied to screen a chemical library against bifunctional AAC(6’)-APH(2’’) enzyme. Using this assay, two pyrimidinyl indole derivatives were found to be potent, and effective AAC(6’)-APH(2’’) inhibitors. The assay of exploring the selective inhibitory effect on two AAC(6’)-APH(2’’) active sites was further performed. Two pyrimidinyl indole derivatives were found to exhibit striking inhibitory activities on AAC(6’).
研究领域:
药理学
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分析化学
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微生物学
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DOI
PubMed
高影响因子
INFECTION GENETICS AND EVOLUTION
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2021
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IF 3.342
Congshan Liu,Jianping Cao,Haobing Zhang,Jianhai Yin
RNA modifications, as one of epigenetic mechanisms, are important and conserved mechanisms for maintaining the homeostasis of organisms. Little is known about RNA modifications in Echinococcus granulosus, an obligate parasite that inhabits mammals and gives rise to a huge public health and economic impact. Here, we focused on the RNA modification characteristics of E. granulosus for the first time by using mass spectrometry (UPLC-MS/MS) to qualitatively and quantitatively analyze 47 types of RNA modifications in E. granulosus total RNA. Furthermore, the E. granulosus homologs of writer enzymes preforming RNA modifications were identified, and their gene expression pattern at different developmental stages were analyzed by bioinformatics analysis. Finally, 23 types of RNA modifications were found in E. granulosus cysts total RNA, of which m 1 A, Ψ and m 5 C are the most abundant. The homologs of writer enzymes involved in these modifications were identified in the E. granulosus genome, with the dynamic gene expression during the different parasitic developmental stages. This work confirms that E. granulosus retains the conserved RNA modification mechanism during evolution, suggesting the important role of RNA modification in regulating its development and parasitic process. Moreover, the differences of amino acid sequences of RNA modification writer enzymes between parasite and host make it possible to use these enzymes as the candidate drug targets in the follow-up in-depth researches.
研究领域:
寄生虫学
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分子生物学
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基因组学
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PubMed
高影响因子
TALANTA
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2021
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IF 6.057
Ning Xia,Ting Sun,Lin Liu,Linxu Tian,Zhifang Sun
Heterogeneous analysis has great application prospects in the detection of post-translational modification (PTM) enzymes with the advantages of signal enhancement, less sample demand, and high sensitivity and selectivity . Nevertheless, once the substrate was fixed on a solid interface, the steric hindrance might limit the approaching of catalytic center to the substrate, thus reducing the efficiency of PTM. Herein, we suggested that the avidin-modified interface could be used to develop heterogeneous sensing platforms with biotin-labeled substrates as the probes, in which the enzymatic PTM was performed in solution and the heterogeneous assay was conducted on a solid surface. The sensing strategy integrates the advantages but overcomes the defects of both homogeneous and heterogeneous assays. Protein kinase A (PKA) and histone acetyltransferase (HAT) were determined as the examples by using sequence-specific peptide substrates. The signal changes were monitored by HRP-based colorimetric assay and antibody-amplified surface plasmon resonance (SPR). The methods were used for analysis of cell lysates and evaluation of inhibition efficiency with satisfactory results. The strategy can be used for the detection of a variety of biological enzymes and provide a new idea for the design of various heterogeneous biosensors. Thus, this work should be of great significance to the popularization and practical application of biosensors.
研究领域:
生物化学
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分子生物学
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分析化学
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生物技术
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DOI
PubMed
高影响因子
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