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11.
Natural products (NPs) are evolutionarily optimized as drug-like molecules and remain the most consistently successful source of drugs and drug leads. They offer major opportunities for finding novel lead structures that are active against a broad spectrum of assay targets, particularly those from secondary metabolites of microbial origin. Due to traditional discovery approaches’ limitations relying on untargeted screening methods, there is a growing trend to employ unconventional secondary metabolomics techniques. Aided by the more in-depth understanding of different biosynthetic pathways and the technological advancement in analytical instrumentation, the development of new methodologies provides an alternative that can accelerate discoveries of new lead-structures of natural origin. This present mini-review briefly discusses selected examples regarding advancements in bioinformatics and genomics (focusing on genome mining and metagenomics approaches), as well as bioanalytics (mass-spectrometry) towards the microbial NPs-based drug discovery and development. The selected recent discoveries from 2015 to 2020 are featured herein. 相似文献
12.
Ntombizethu Nokuphiwa Msomi Tiara Padayachee Nomfundo Nzuza Puleng Rosinah Syed Justyna Dorota Kry Wanping Chen Dominik Gront David R. Nelson Khajamohiddin Syed 《Molecules (Basel, Switzerland)》2021,26(6)
The impact of lifestyle on shaping the genome content of an organism is a well-known phenomenon and cytochrome P450 enzymes (CYPs/P450s), heme-thiolate proteins that are ubiquitously present in organisms, are no exception. Recent studies focusing on a few bacterial species such as Streptomyces, Mycobacterium, Cyanobacteria and Firmicutes revealed that the impact of lifestyle affected the P450 repertoire in these species. However, this phenomenon needs to be understood in other bacterial species. We therefore performed genome data mining, annotation, phylogenetic analysis of P450s and their role in secondary metabolism in the bacterial class Gammaproteobacteria. Genome-wide data mining for P450s in 1261 Gammaproteobacterial species belonging to 161 genera revealed that only 169 species belonging to 41 genera have P450s. A total of 277 P450s found in 169 species grouped into 84 P450 families and 105 P450 subfamilies, where 38 new P450 families were found. Only 18% of P450s were found to be involved in secondary metabolism in Gammaproteobacterial species, as observed in Firmicutes as well. The pathogenic or commensal lifestyle of Gammaproteobacterial species influences them to such an extent that they have the lowest number of P450s compared to other bacterial species, indicating the impact of lifestyle on shaping the P450 repertoire. This study is the first report on comprehensive analysis of P450s in Gammaproteobacteria. 相似文献
13.
对原核生物基因组的研究显示,基因组GC含量与基因组大小和氧气偏好性等因素存在着一定的相关性。为了探索基因组大小与GC含量的相关性是否受原核生物生活习性的影响,选取了有代表性的411种原核生物(包括古细菌与真细菌),分别从最适生长温度、氧气偏好性、运动特性、水生特性和寄生特性等因素进行分析,发现基因组大小与GC含量的相关性确实受这些因素的影响,而寄生原核生物中显示出最好的相关性。 相似文献
14.
Michio Kurosu Katsuhiko Mitachi Junshu Yang Edward V. Pershing Bruce D. Horowitz Eric A. Wachter John W. Lacey III Yinduo Ji Dominic J. Rodrigues 《Molecules (Basel, Switzerland)》2022,27(1)
Rose bengal has been used in the diagnosis of ophthalmic disorders and liver function, and has been studied for the treatment of solid tumor cancers. To date, the antibacterial activity of rose bengal has been sporadically reported; however, these data have been generated with a commercial grade of rose bengal, which contains major uncontrolled impurities generated by the manufacturing process (80–95% dye content). A high-purity form of rose bengal formulation (HP-RBf, >99.5% dye content) kills a battery of Gram-positive bacteria, including drug-resistant strains at low concentrations (0.01–3.13 μg/mL) under fluorescent, LED, and natural light in a few minutes. Significantly, HP-RBf effectively eradicates Gram-positive bacterial biofilms. The frequency that Gram-positive bacteria spontaneously developed resistance to HP-RB is extremely low (less than 1 × 10−13). Toxicity data obtained through our research programs indicate that HP-RB is feasible as an anti-infective drug for the treatment of skin and soft tissue infections (SSTIs) involving multidrug-resistant (MDR) microbial invasion of the skin, and for eradicating biofilms. This article summarizes the antibacterial activity of pharmaceutical-grade rose bengal, HP-RB, against Gram-positive bacteria, its cytotoxicity against skin cells under illumination conditions, and mechanistic insights into rose bengal’s bactericidal activity under dark conditions. 相似文献
15.
Kinga Vojnits Mio Nakanishi Deanna Porras Yeonjoon Kim Zhuohang Feng Diana Golubeva Mick Bhatia 《Molecules (Basel, Switzerland)》2022,27(8)
Application of the CRISPR/Cas9 system to knock in fluorescent proteins to endogenous genes of interest in human pluripotent stem cells (hPSCs) has the potential to facilitate hPSC-based disease modeling, drug screening, and optimization of transplantation therapy. To evaluate the capability of fluorescent reporter hPSC lines for high-content screening approaches, we targeted EGFP to the endogenous OCT4 locus. Resulting hPSC–OCT4–EGFP lines generated expressed EGFP coincident with pluripotency markers and could be adapted to multi-well formats for high-content screening (HCS) campaigns. However, after long-term culture, hPSCs transiently lost their EGFP expression. Alternatively, through EGFP knock-in to the AAVS1 locus, we established a stable and consistent EGFP-expressing hPSC–AAVS1–EGFP line that maintained EGFP expression during in vitro hematopoietic and neural differentiation. Thus, hPSC–AAVS1–EGFP-derived sensory neurons could be adapted to a high-content screening platform that can be applied to high-throughput small-molecule screening and drug discovery campaigns. Our observations are consistent with recent findings indicating that high-frequency on-target complexities appear following CRISPR/Cas9 genome editing at the OCT4 locus. In contrast, we demonstrate that the AAVS1 locus is a safe genomic location in hPSCs with high gene expression that does not impact hPSC quality and differentiation. Our findings suggest that the CRISPR/Cas9-integrated AAVS1 system should be applied for generating stable reporter hPSC lines for long-term HCS approaches, and they underscore the importance of careful evaluation and selection of the applied reporter cell lines for HCS purposes. 相似文献
16.
亚硝胺类化合物诱导小鼠食管病变与基因组甲基化的关系研究 总被引:1,自引:0,他引:1
研究亚硝胺类化合物诱导小鼠食管发生病变与基因甲基化的关系,在亚硝酸钠(NaNO2)和N,N-二甲基苄胺(N,N-Dimethylbenzylamine)混合物诱导小鼠食管病变过程中,定期取小鼠食管,一部分做病理切片观察组织学变化;另一部分提取组织DNA做变性高效液相色谱(Denaturing High Performance Liquid Chromatography,DHPLC),检测基因组甲基化修饰的改变。结果在亚苄混合物诱导的小鼠食管癌变过程中,全基因组甲基化修饰是逐渐降低的,在达到一定程度后即保持一种稳态。此时组织病理学才发生光镜下可见的改变。说明全基因组甲基化修饰的逐渐降低可能是亚硝胺类化合物诱导食管发生病变的途径之一.这种基因修饰的变化有助于进一步研究食管鳞癌发生的分子机制。 相似文献
17.
艾对元 《兰州大学学报(自然科学版)》2009,45(Z1)
病毒基因组中的重复序列比率很低,因为其核酸序列大都是编码区域.如果出现一段同向对称或者是反向对称序列在病毒基因组中,它往往代表一个调控元件,或者是一个信号因子.我们总结了病毒中的一些对称序列,并阐明它的特点,分布及功能. 相似文献
19.
Comparative analysis of A,B,C and D genomes in the genus Oryza with C_0t-1 DNA of C genome 总被引:1,自引:0,他引:1
LAN Weizhen* QIN Rui * LI Gang & HE Guangcun. Key Laboratory of State Ethnic Affairs Commission for Biological Technology College of Life Sciences South-Central University for Nationalities Wuhan China . Key Laboratory of Ministry of Education for Plant Developmental Biology College of Life Sciences Wuhan University Wuhan China 《科学通报(英文版)》2006,51(14)
The genus Oryza includes two cultivated species, O. sativa L. and O. glaberrima Steud. and comprises more than 20 species[1]. The genomes of Oryza are classified into 10 types: AA, BB, CC, BBCC, CCDD, EE, FF, GG, HHJJ and HHKK[2,3]. Morphological variatio… 相似文献
20.