Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 24
Filtrar
1.
J Nat Prod ; 87(2): 424-438, 2024 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-38289177

RESUMEN

Ever since the isolation of Amycolatopsis mediterranei in 1957, this strain has been the focus of research worldwide. In the last 60 years or more, our understanding of the taxonomy, development of cloning vectors and conjugation system, physiology, genetics, genomics, and biosynthetic pathway of rifamycin B production in A. mediterranei has substantially increased. In particular, the development of cloning vectors, transformation system, characterization of the rifamycin biosynthetic gene cluster, and the regulation of rifamycin B production by the pioneering work of Heinz Floss have made the rifamycin polyketide biosynthetic gene cluster (PKS) an attractive target for extensive genetic manipulations to produce rifamycin B analogues which could be effective against multi-drug-resistant tuberculosis. Additionally, a better understanding of the regulation of rifamycin B production and the application of newer genomics tools, including CRISPR-assisted genome editing systems, might prove useful to overcome the limitations associated with low production of rifamycin analogues.


Asunto(s)
Actinomycetales , Rifamicinas , Amycolatopsis , Vías Biosintéticas/genética , Rifamicinas/metabolismo
2.
Funct Integr Genomics ; 23(3): 231, 2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37432480

RESUMEN

Monkeypox is a viral zoonosis with symptoms that are reminiscent of those experienced in previous smallpox cases. The GSAID database (Global Initiative on Sharing Avian Influenza Data) was used to assess 630 genomes of MPXV. The phylogenetic study revealed six primary clades, as well as a smaller percentage in radiating clades. Individual clades that make up various nationalities may have formed as a result of a particular SNP hotspot type that mutated in a specific population. The most significant mutation based on a mutational hotspot analysis was found at G3729A and G5143A. The gene ORF138, which encodes the Ankyrin repeat (ANK) protein, was found to have the most mutations. This protein mediates molecular recognition via protein-protein interactions. It was shown that 243 host proteins interacted with 10 monkeypox proteins identified as the hub proteins E3, SPI2, C5, K7, E8, G6, N2, B14, CRMB, and A41 through 262 direct connections. The interaction with chemokine system-related proteins provides further evidence that the monkeypox virus suppresses human proteins to facilitate its survival against innate immunity. Several FDA-approved molecules were evaluated as possible inhibitors of F13, a significant envelope protein on the membrane of extracellular versions of the virus. A total of 2500 putative ligands were individually docked with the F13 protein. The interaction between the F13 protein and these molecules may help prevent the monkeypox virus from spreading. After being confirmed by experiments, these putative inhibitors could have an impact on the activity of these proteins and be used in monkeypox treatments.


Asunto(s)
Monkeypox virus , Mpox , Animales , Humanos , Filogenia , Genómica , Mutación
3.
Neuroimmunomodulation ; 30(1): 196-205, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37336193

RESUMEN

The assumption of the pineal hormone melatonin as a therapeutic use for COVID-19-affected people seems promising. Its intake has shown significant improvement in the patients' conditions. Higher melatonin titers in children may provide a protective shield against this disease. The hormone melatonin works as an anti-inflammatory, antioxidant, immunomodulator, and strategically slows down the cytokine release which is observed in the COVID-19 disease, thereby improving the overall health of afflicted patients. The medical community is expected shortly to use remedial attributes like anti-inflammatory, antioxidant, antivirals, etc., of melatonin in the successful prevention and cure of COVID-19 morbidity. Thus, the administration of melatonin seems auspicious in the cure and prevention of this COVID-19 fatality. Moreover, melatonin does not seem to reduce the efficiency of approved vaccines against the SARS-CoV-2 virus. Melatonin increases the production of inflammatory cytokines and Th1 and enhances both humoral and cell-mediated responses. Through the enhanced humoral immunity, melatonin exhibits antiviral activities by suppressing multiple inflammatory products such as IL-6, IL1ß, and tumor necrosis factor α, which are immediately released during lung injury of severe COVID-19. Hence, the novel use of melatonin along with other antivirals as an early treatment option against COVID-19 infection is suggested. Here, we have chalked out the invasion mechanisms and appropriate implications of the latest findings concerned with melatonin against the virus SARS-CoV-2. Nevertheless, within the setting of a clinical intervention, the promising compounds must go through a series of studies before their recommendation. In the clinical field, this is done in a time-ordered sequence, in line with the phase label affixed to proper protocol of trials: phase I-phase II and the final phase III. Nevertheless, while medical recommendations can only be made on the basis of reassuring evidence, there are still three issues worth considering before implementation: representativeness, validity, and lastly generalizability.


Asunto(s)
COVID-19 , Melatonina , Niño , Humanos , Melatonina/uso terapéutico , SARS-CoV-2 , Antioxidantes/uso terapéutico , Antivirales/uso terapéutico , Antiinflamatorios/uso terapéutico
4.
Environ Res ; 238(Pt 1): 117140, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-37716389

RESUMEN

The Najafgarh drain plays a significant role in the pollution of the Yamuna River, accounting for 40% of the total pollution. Therefore, it is crucial to investigate and analyze the microbial diversity, metabolic functional capacity, and antibiotic resistance genes (ARGs) present in the Najafgarh drain. Additionally, studying the water quality and its relationship with the proliferation of microorganisms in the drain is of utmost importance. Results obtained confirmed the deteriorated water quality as physico-chemical parameters such as biochemical oxygen demand (BOD), chemical oxygen demand (COD), dissolved oxygen (DO), and total suspended solids (TSS) in the range of 125-140, 400-460, 0-0.2, 25-140.4 mg/l respectively violated the standard permissible national and global standards. In addition, the next generation sequencing (NGS) analysis confirm the presence of genus such as Thauera, Arcobacter, Pseudomonas, Geobacter, Dechloromonas, Tolumonas, Sulfurospirullum, Desulfovibrio, Aeromonas, Bacteroides, Prevotella, Cloacibacterium, Bifidobacterium, Clostridium etc. along with 864 ARGs in the wastewater obtained from the Najafgarh drain. Findings confirm that the pathogenic species reported from this dataset possess severe detrimental impact on faunal and human health. Further, Pearson's r correlation analysis indicated that environmental variables, mainly total dissolved solids (TDS) and chemical oxygen demand (COD), play a pivotal role in driving microbial community structure of this heavily polluted drain. Thus, the poor water quality, presence of a microbial nexus, pathogenic markers, and ARGs throughout this drain confirmed that it would be one potential contributor to the dissemination of disease-causing agents (pathogens) to the household and drinking water supplies in the near future.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Humanos , Antibacterianos/farmacología , Calidad del Agua , Análisis de la Demanda Biológica de Oxígeno , Abastecimiento de Agua
5.
Indian J Microbiol ; 63(3): 244-252, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37781004

RESUMEN

The art of utilizing and manipulating micro materials have been dated back to antient era. With the advancement in technologies, the state-of-art methods of nano technologies and nano sciences has been employed in various sectors including environment, product designing, food industry, pharmaceuticals industries to way out solve standard problem of mankind. Due to rapid industrialization and the alarming levels of pollution there has been an urgent need to address the environmental and energy issues. Environmental sustainability concerns the global climate change and pollution including air, water, soil. The field of nanotechnology has proven to be a promising field where sensing and remediation, have been dramatically advanced by the use of nanomaterials. This emergent science of surface to mass ratio is the principle theorem for manipulating structure at molecular levels. The review sums up all the advancements in the field of nanotechnology and their recent application in the environment. New opportunities and challenges have also been discussed in detail to understand the use of nanotechnology as problem-to-solution ratio. Graphical abstract: Image depicting the application of nanotechnology in environmental concerns. The combinations of technologies like bioremediations, bioaugmentations with state-of-the-art nanotechnology like carbon nanotubes and Nano capsules to answer the environmental challenges of soil quality, and plant productivity.

6.
Indian J Microbiol ; 62(3): 323-337, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35974919

RESUMEN

A rigorous exploration of microbial diversity has revealed its presence on Earth, deep oceans, and vast space. The presence of microbial life in diverse environmental conditions, ranging from moderate to extreme temperature, pH, salinity, oxygen, radiations, and altitudes, has provided the necessary impetus to search for them by extending the limits of their habitats. Microbiology started as a distinct science in the mid-nineteenth century and has provided inputs for the betterment of mankind during the last 150 years. As beneficial microbes are assets and pathogens are detrimental, studying both have its own merits. Scientists are nowadays working on illustrating the microbial dynamics in Earth's subsurface, deep sea, and polar regions. In addition to studying the role of microbes in the environment, the microbe-host interactions in humans, animals and plants are also unearthing newer insights that can help us to improve the health of the host by modulating the microbiota. Microbes have the potential to remediate persistent organic pollutants. Antimicrobial resistance which is a serious concern can also be tackled only after monitoring the spread of resistant microbes using disciplines of genomics and metagenomics The cognizance of microbiology has reached the top of the world. Space Missions are now looking for signs of life on the planets (specifically Mars), the Moon and beyond them. Among the most potent pieces of evidence to support the existence of life is to look for microbial, plant, and animal fossils. There is also an urgent need to deliberate and communicate these findings to layman and policymakers that would help them to take an adequate decision for better health and the environment around us. Here, we present a glimpse of recent advancements by scientists from around the world, exploring and exploiting microbial diversity.

7.
Artículo en Inglés | MEDLINE | ID: mdl-34236299

RESUMEN

Deinococcus species are widely studied due to their utility in bioremediation of sites contaminated with radioactive elements. In the present study, we re-evaluated the taxonomic placement of two species of the genus Deinococcus namely D. swuensis DY59T and D. radiopugnans ATCC 19172T based on whole genome analyses. The 16S rRNA gene analysis revealed a 99.58% sequence similarity between this species pair that is above the recommended threshold value for species delineation. These two species also clustered together in both the 16S rRNA gene and core genome based phylogenies depicting their close relatedness. Furthermore, more than 98% of genes were shared between D. swuensis DY59T and D. radiopugnans ATCC 19172T. Interestingly, D. swuensis DY59T and D. radiopugnans ATCC 19172T shared high genome similarity in different genomic indices. They displayed an average nucleotide identity value of 97.63%, an average amino acid identity value of 97% and a digital DNA-DNA hybridization value equal to 79.50%, all of which are well above the cut-off for species delineation. Altogether, based on these evidences, D. swuensis DY59T and D. radiopugnans ATCC 19172T constitute a single species. Hence, as per the priority of publication, we propose that Deinococcus swuensis Lee et al. 2015 should be reclassified as a later heterotypic synonym of Deinococcus radiopugnans.


Asunto(s)
Deinococcus/clasificación , Filogenia , Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Genómica , Hibridación de Ácido Nucleico , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN
8.
Indian J Microbiol ; 60(1): 37-44, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32089572

RESUMEN

The term hygiene is deeply rooted with the concept of maintaining sound health and alertness towards cleanliness, while "hygiene hypothesis" depicts the protective role of microbial community exposure in development of early immunity and initial allergic and aesthetic reactions. The tug-of-war has now been pushed toward the literal term "hygiene" over the "hygiene hypothesis" and has continued with disinfection of all microbial loads from the related environments to avoid infections in humans. With the advancement in the microbiome studies, it became clear that humans possess warm, and significant relationships with diverse microbial community. With this opinion article, we have emphasized on the importance of hygiene hypothesis in immunological responses. We also propose the individual/targeted hygiene instead of application of unanimous hygiene hypothesis. This review also elaborates the common practices that should be employed to maintain hygiene along with the balanced microbiome.

9.
Indian J Microbiol ; 60(3): 310-317, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32655198

RESUMEN

Amycolatopsis mediterranei S699 produces rifamycin B and successors of this strain are in use for the industrial production of rifamycin B. Semisynthetic derivatives of rifamycin B are used against Mycobacterium tuberculosis that causes tuberculosis. Although the rifamycin biosynthetic gene cluster was characterized two decades ago, the regulation of rifamycin B biosynthesis in Amycolatopsis mediterranei S699 is poorly understood. In this study, we analysed the genome and proteome of Amycolatopsis mediterranei S699 and identified 1102 transcription factors which comprise about 10% of the total genome. Using interactomics approaches we delineated 30 unique transcription factors directly involved in secondary metabolism that regulate rifamycin B biosynthesis. We also predict the role of RifN as hub in controlling the regulation of other genes involved in rifamycin biosynthesis. RifN is important for maintaining the integrity of the rifamycin-network. Thus, these transcription factor can be exploited to improve rifamycin B production in Amycolatopsis mediterranei S699.

10.
Indian J Microbiol ; 60(1): 26-36, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32089571

RESUMEN

The gut microbiome analysis, with specific interest on their direct impact towards the human health, is currently revolutionizing the unexplored frontiers of the pathogenesis and wellness. Although in-depth investigations of gut microbiome, 'the Black Boxes', complexities and functionalities are yet at its infancy, profound evidences are being reported for their concurrent involvement in disease etiology and its treatment. Interestingly, studies from the 'minimal murine' (Oligo-MM12), 'humanized' microbiota gnotobiotic mice models and patient samples, combined with multi-omics and cell biology approaches, have been revealing the implications of these findings in the treatment of gut dysbiosis associated diseases. Nonetheless, due to the inherent heterogeneity of the gut commensals and their unified co-existence with opportunistic pathobionts, it is utmost essential to highlight their functionalities in 'good or bad' gut in human wellness. We have specifically reviewed dietary lifestyle and infectious diseases linked with the gut bacterial consortia to delineate the ecobiotic approaches towards their treatment. This notably includes gut mucosal immunity mediated diseases such as Tuberculosis, IBD, CDI, Type 2 Diabetes, etc. Alongside of each dysbiosis, we have described the current therapeutic advancements of the pre- and probiotics derived from human microbiome studies to restore gut microbial homeostasis. With a continuous running debate on the role of microbiota in above mentioned diseases, we have collected numerous scientific evidences highlighting a previously unanticipated complex involvement of gut microbiome in the potential of human health.

11.
Antonie Van Leeuwenhoek ; 110(10): 1357-1371, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28831610

RESUMEN

The current prokaryotic taxonomy classifies phenotypically and genotypically diverse microorganisms using a polyphasic approach. With advances in the next-generation sequencing technologies and computational tools for analysis of genomes, the traditional polyphasic method is complemented with genomic data to delineate and classify bacterial genera and species as an alternative to cumbersome and error-prone laboratory tests. This review discusses the applications of sequence-based tools and techniques for bacterial classification and provides a scheme for more robust and reproducible bacterial classification based on genomic data. The present review highlights promising tools and techniques such as ortho-Average Nucleotide Identity, Genome to Genome Distance Calculator and Multi Locus Sequence Analysis, which can be validly employed for characterizing novel microorganisms and assessing phylogenetic relationships. In addition, the review discusses the possibility of employing metagenomic data to assess the phylogenetic associations of uncultured microorganisms. Through this article, we present a review of genomic approaches that can be included in the scheme of taxonomy of bacteria and archaea based on computational and in silico advances to boost the credibility of taxonomic classification in this genomic era.


Asunto(s)
Archaea/clasificación , Bacterias/clasificación , Técnicas de Tipificación Bacteriana , Biología Computacional , Genómica , Genoma Arqueal/genética , Genoma Bacteriano/genética , Metagenoma , Anotación de Secuencia Molecular , Filogenia
14.
3 Biotech ; 13(1): 34, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36619820

RESUMEN

The present study scrutinizes the presence of Streptomyces strains in the soil sample collected from industrial area of Bahadurgarh (Haryana) India. The morphological approach manifested the isolated strain belong to Streptomyces species and named as Streptomyces sp. KD18. Sequencing of Streptomyces sp. KD18 genome was performed by Illumina Nextseq500 platform. 65 contigs were generated via SPAdes v3.11.1 and harboured genome size of 7.2 Mb. AntiSMASH server revealed the presence of 25 biosynthetic gene clusters in KD18 genome where BGC of lipstatin was of more interest from industrial and pharmaceutical purpose. The draft genome sequence represented via ANI values claimed that the KD18 strain belongs to Streptomyces toxytricini and finally named as S. toxytricini KD18. The LC-MS analysis of the extracted metabolite confirmed the production of lipstatin. The genome sequence data have been deposited to NCBI under the accession number of GCA_014748315.1. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03453-3.

15.
Mol Biotechnol ; 2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36913083

RESUMEN

Implementation of computational tools in the identification of novel drug targets for Tuberculosis (TB) has been a promising area of research. TB has been a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) localized primarily on the lungs and it has been one of the most successful pathogen in the history of mankind. Extensively arising drug resistivity in TB has made it a global challenge and need for new drugs has become utmost important.The involvement of Nucleoid-Associated Proteins (NAPs) in maintaining the structure of the genomic material and regulating various cellular processes like transcription, DNA replication, repair and recombination makes significant, has opened a new arena to find the drugs targeting Mtb. The current study aims to identify potential inhibitors of NAPs through a computational approach. In the present work we worked on the eight NAPs of Mtb, namely, Lsr2, EspR, HupB, HNS, NapA, mIHF and NapM. The structural modelling and analysis of these NAPs were carried out. Moreover, molecular interaction were checked and binding energy was identified for 2500 FDA-approved drugs that were selected for antagonist analysis to choose novel inhibitors targeting NAPs of Mtb. Drugs including Amikacin, streptomycin, kanamycin, and isoniazid along with eight FDA-approved molecules that were found to be potential novel targets for these mycobacterial NAPs and have an impact on their functions. The potentiality of several anti-tubercular drugs as therapeutic agents identified through computational modelling and simulation unlocks a new gateway for accomplishing the goal to treat TB. Complete framework of the methodology employed in this study to predict inhibitors against mycobacterial NAPs.

16.
J Biomol Struct Dyn ; 41(22): 12632-12642, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36644882

RESUMEN

The gut bacterial strains and their metabolites have been shown to play a significant role in obesity, but the molecular mechanisms underlying this association are largely unresolved. Obesity is a multifactorial problem and is controlled by various mechanisms and pathways to produce and store fat cells. Bacteriocins are secondary metabolites produced by gut bacteria to defend themselves against their competitors. Recently, they have gained great attention due to their role in metabolic disorders, including obesity. Stearoyl-CoA desaturase 1 (SCD1) is a key enzyme involved in the differentiation of adipocytes. The aim of this study is to show the regulation of SCD1 by bacteriocins and thus their importance in obesity control. We screened the human gut bacteriome for the presence of bacteriocins, predicted their structures, and showed their inhibitory role by molecular docking with SCD1. Further, to confirm the docking results, MDS of six top scoring SCD1-bacteriocin complexes were carried out for 100 ns. These six bacteriocins namely, Plantaricin S-beta, Carnolysin, Lactococcin B, Bacteriocin Iic, Plantaricin N, and Thermophilin A, with strong binding affinities, are primarily produced by bacterial strains from the Lactobacillaeacea family. These findings can be the basis of further experiments for enhanced understanding of the underlying mechanisms for obesity control, specifically bacteriocins driven regulation of the SCD1 enzyme. In addition, a consortium of bacterial strains producing these bacteriocins can be developed and used as probiotics for the amelioration of obesity and other metabolic complications.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Bacteriocinas , Microbioma Gastrointestinal , Humanos , Estearoil-CoA Desaturasa/metabolismo , Simulación del Acoplamiento Molecular , Obesidad , Diferenciación Celular , Adipocitos/metabolismo , Termogénesis/fisiología , Bacteriocinas/farmacología , Bacteriocinas/metabolismo
17.
Discov Nano ; 18(1): 158, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-38123864

RESUMEN

The initiation of the "nanotechnology era" within the past decade has been prominently marked by advancements in biomaterials. This intersection has opened up numerous possibilities for enhancing the detection, diagnosis, and treatment of various illnesses by leveraging the synergy between biomaterials and nanotechnology. The term "nano biomaterials" referring to biomaterials featuring constituent or surface feature sizes below 100 nm, presents a realm of extraordinary materials endowed with unique structures and properties. Beyond addressing common biomedical challenges, these nano biomaterials contribute unprecedented insights and principles that enrich our understanding of biology, medicine, and materials science. A critical evaluation of recent technological progress in employing biomaterials in medicine is essential, along with an exploration of potential future trends. Nanotechnology breakthroughs have yielded novel surfaces, materials, and configurations with notable applications in the biomedical domain. The integration of nanotechnology has already begun to enhance traditional biomedical practices across diverse fields such as tissue engineering, intelligent systems, the utilization of nanocomposites in implant design, controlled release systems, biosensors, and more. This mini review encapsulates insights into biomaterials, encompassing their types, synthesis methods, and the roles of organic and inorganic nanoparticles, elucidating their mechanisms of action. Furthermore, the focus is squarely placed on nano biomaterials and their versatile applications, with a particular emphasis on their roles in anticancer and antimicrobial interventions. This review underscores the dynamic landscape of nanotechnology, envisioning a future where nano biomaterials play a pivotal role in advancing medical applications, particularly in combating cancer and microbial infections.

18.
3 Biotech ; 13(6): 168, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37188288

RESUMEN

Mycobacterial species is known for inhabiting various niches ranging from soil to harsh intracellular environment of animal hosts and their survival through constant changes. For survival and persistence, these organisms must quickly adapt by bringing shift in their metabolism. Metabolic shifts are brought by sensing the environmental cues usually by membrane localized sensor molecules. These signals are transmitted to regulators of various metabolic pathways leading to post-translational modifications of regulators ultimately resulting in altered metabolic state of the cell. Multiple regulatory mechanisms have been unearthed so far that play crucial role in adapting to these situations, and among them, the signal-dependent transcriptional regulators mediated responses are integral for the microbes to perceive environmental signals and generate appropriate adaptive responses. LysR-type transcriptional regulators (LTTRs) form the largest family of transcriptional regulators, which are present in all kingdoms of life. Their numbers vary among bacterial genera and even in different mycobacterial species. To understand the evolutionary aspect of pathogenicity based on LTTRs, we performed phylogenetic analysis of LTTRs encoded by several mycobacterial species representing non-pathogenic (NP), opportunistic (OP), and totally pathogenic (TP) mycobacteria. Our results showed that LTTRs of TP clustered separately from LTTRs of NP and OP mycobacteria. In addition, LTTRs frequency per Mb of genome was reduced in TP when compared with NP and OP. Further, the protein-protein interactions and degree-based network analysis showed concomitant increased interactions per LTTRs with increase in pathogenicity. These results suggested the increase in regulon of LTTRs during evolution of TP mycobacteria.

19.
mSystems ; 6(4): e0086221, 2021 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-34427500

RESUMEN

Secondary metabolites produced by Actinobacteria are an important source of antibiotics, drugs, and antimicrobial peptides. However, the large genome size of actinobacteria with high gene coding density makes it difficult to understand the complex regulation of biosynthesis of such critically and economically important products. In the last few decades, apart from genomics sequences, high-throughput proteomics has proven beneficial to understand the key players regulating the expression pattern of secondary metabolite and antibiotic production in different experimental set-ups. In the past, we have been analyzing the genomics data and mass spectrometry-based proteomics to predict the regulation dynamics and crucial regulatory hubs in Actinobacteria. The multidirectional regulation and expression of the biosynthetic gene cluster responsible for the production of important metabolite take their cue from the other primary metabolism pathways with which they show intricate interactions in the interactome. The regulation occurs by not only the action and expression of the biosynthetic gene cluster but also the role of transcription factors and primary metabolic pathways. Using the key players of these interactomes, we can regulate the synthesis/production of these valuable peptides/metabolites. Simultaneously, the multi-omics approach has now opened new gateways in investigation, screening, and identification of naturally occurring antimicrobial peptides from actinobacteria which are beneficial for humans and also provide economic and industrial benefits to humankind.

20.
J Proteomics ; 239: 104168, 2021 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-33662614

RESUMEN

Rifamycin B is produced by Amycolatopsis mediterranei S699 as a secondary metabolite. Its semi-synthetic derivatives have been used for curing tuberculosis caused by Mycobacterium tuberculosis. But the emergence of rifampicin-resistant strains required analogs of rifamycin B to be developed by rifamycin biosynthetic gene cluster manipulation. In 2014 genetic engineering of the rifamycin polyketide synthase gene cluster in S699 led to a mutant, A. mediterranei DCO#34, that produced 24-desmethylrifamycin B. Unfortunately, the productivity was strongly reduced to 20 mgL-1 as compared to 50 mgL-1 of rifamycin B. To understand the mechanisms leading to reduced productivity and rifamycin biosynthesis by A. mediterranei S699 during the early and late growth phase we performed a proteome study for wild type strain S699, mutant DCO#34, and the non-producer strain SCO2-2. Proteins identification and relative label-free quantification were performed by nLC-MS/MS. Data are available via ProteomeXchange with identifier PXD016416. Also, in-silico protein-protein interaction approach was used to determine the relationship between different structural and regulatory proteins involved in rifamycin biosynthesis. Our studies revealed RifA, RifK, RifL, Rif-Orf19 as the major regulatory hubs. Relative abundance expression values revealed that genes encoding RifC-RifI and the transporter RifP, down-regulated in DCO#34 and genes encoding RifR, RifZ, other regulatory proteins up-regulated. SIGNIFICANCE: The study is designed mainly to understand the underlying mechanisms of rifamycin biosynthesis in Amycolatopsis mediterranei. This resulted in the identification of regulatory hubs which play a crucial role in regulating secondary metabolism. It elucidates the complex mechanism of secondary metabolite biosynthesis and their conversion and extracellular transportation in temporal correlation with the different growth phases. The study also elucidated the mechanisms leading to reduced production of analog, 24-desmethylrifamycin B by the genetically modified strain DCO#34, derivatives of which have been found effective against rifampicin-resistant strains of Mycobacterium tuberculosis. These results can be useful while carrying out genetic manipulations to improve the strains of Amycolatopsis to produce better analogs/drugs and promote the eradication of TB. Thus, this study is contributing significantly to the growing knowledge in the field of the crucial drug, rifamycin B biosynthesis by an economically important bacterium Amycolatopsis mediterranei.


Asunto(s)
Proteoma , Rifamicinas , Amycolatopsis , Espectrometría de Masas en Tándem
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA