scholarly journals Genome Analysis of The Salt-Resistant Paludifilum Halophilum DSM 102817T Reveals Genes Involved In Flux-Tuning of Ectoines And Unexplored Bioactive Secondary Metabolites

Author(s):  
Donyez Frikha-Dammak ◽  
Houda Ayadi ◽  
Imen Hakim Rekik ◽  
Lassaad Belbahri ◽  
Sami Maalej

Abstract Paludifilum halophilum is the first member of the genus Paludifilum in the Thermoactinomycetaceae family. The thermohalophilic bacterium was isoated from the solar saltern of Sfax, in Tunisia and was shown to be able to produce ectoines in relatively high-yield and cope with salt stress conditions. In this study, the whole genome of P. halophilum was sequenced and analysed. Analysis revealed 3,789,765 base pairs with average GC % content of 51.5%. A total of 3,775 genes were predicted of which 3616 were protein-coding genes and 73 were RNA genes. The genes encoding key enzymes for ectoines synthesis were identified from the bacterial genome next to a gene cluster (ehuABCD) encoding a binding-protein-dependent ABC transport system responsible for ectoines mobility through the cell membrane. With the aid of KEGG analysis, we found that the central catabolic network of P. halophilum comprises the pathways of glycolysis, tricarboxylic acid (TCA) cycle, and pentose phosphate pathway (PPP). In addition, anaplerotic pathways replenishing oxaloacetate and glutamate synthesis from central metabolism, both needed for high ectoines biosynthetic fluxes were identified through several key enzymes. Furthermore, a total of 18 antiSMASH-predicted putative biosynthetic gene clusters (BGCs) for secondary metabolites with high novelty and diversity were identified in P. halophilum genome, including biosynthesis of Colabomycine-A, Fusaricidin-E, Zwittermycin A, Streptomycin, Mycosubtilin and Meilingmycin. Based on these data, P. halophilum emerged as a promising source for ectoines and antimicrobials with the potential to be scaled up for industrial production, which could benefit the pharmaceutical and cosmetic industries.

2021 ◽  
Author(s):  
Veilumuthu P ◽  
Nagarajan T ◽  
Sasikumar S ◽  
Siva R ◽  
J Godwin Christopher

Abstract Streptomyces species is one among the dominant group of bacteria in the family Actinobacteria with a rich repertoire of secondary metabolites. Secondary metabolites with antimicrobial activity and plant growth promotor have been isolated from various Streptomyces sp. Here in this investigation, we present the draft genome of a new species, Streptomyces sp. VITGV156 isolated from healthy tomato plant (Lycopersicon esculentum) which has some rare antimicrobial secondary metabolites, like coelichelin, fluostatins, vicenistatin, nystatin, sipanmycin, and informatipeptin. The genome is 8.18 Mb in size with 6,259 protein coding genes. The average GC content of the genome is 72.61 %. Preliminary analysis with antiSMASH 6.0 revealed the presence of 29 biosynthetic gene clusters for the synthesis of potential secondary metabolites. These includes 4 NRPS (non – ribosomal peptide synthetase), 7 PKS (Polyketide Synthases), 2 RiPP (Ribosomally synthesized and post-translationally modified peptides) clusters. When we look into genes associated with secondary metabolites, 406 genes are present which includes 184 genes for cofactor and vitamins, 72 genes for terpenoids and polyketides, 70 genes for xenobiotics and 80 genes for other metabolites are present. Comparative genome analysis of VITGV156 with its closest neighbor Streptomyces luteus strain TRM45540 revealed ANI 91.22% and dDDH value 44.00%.


2021 ◽  
Vol 18 (4) ◽  
pp. 709-721
Author(s):  
Le Ngoc Giang ◽  
Le Thi Hong Minh ◽  
Vu Thi Quyen ◽  
Nguyen Mai Anh ◽  
Nguyen Thi Kim Cuc ◽  
...  

The streptomyces is one of the best characterized ubiquitous filamentous bacteria from the actinobacteriaclass. They are known to produce thousands of specialized metabolite biosynthesis gene clusters (SMBG). Their SMBG clusters have multiple activities ranging from antimicrobial, antitumor, antiviral and probiotic. Streptomyces strain and their isolates with interesting biological activities against gram-positive and gram-negative indicator strains was recently characterised. Currently, they are employed in more than half of all antibiotics used in human and veterinary medicine. With the increase in drug resistance bacteria, it is important to mine for new natural chemicals.In this study, screening via disk-diffusion agar method revealed that Streptomyces sp. PDH23 isolated from the Rhabdastrellaglobostellata marine sponge sample from Da Nang, Vietnam produce antimicrobial agents with a wide spectrum of activities. This species can produce highly active enzymes, which breakdown celluloses, amyloses and proteins. On top of that they are shown to restrict the grow of the gram positive Bacillus cereus ATCC14579 (BC), Staphylococcus aureus ATCC25923 (SA), the gram-negativeVibrio parahaemolyticus ATCC17802 (VP) and the Candida albicans ATCC10231 fungus (CA). They are antimethicillin-resistant S. aureus(MRSA) ATCC33591 andmethicillin-resistantS. epidermidis (MRSE) ATCC35984. The taxonomy of PDH23 was characterized using 16S rRNA analysis. Whole genome sequencing of PDH23 showed 8594820 base pairs with GC content of 72.03%. Mining of secondary metabolites reveals gene clusters responsible for the biosynthesis of known and/or novel secondary metabolites, including different types of terpene, NRPS-like , PKS, PKS-like, hglE-KS, betalactone, melanin, t1pks, t2pks, t3pks, nrps, indole, siderophore, bacteriocin, ectoine, butyrolactone, phenazine.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3738 ◽  
Author(s):  
Juwairiah Remali ◽  
Nurul ‘Izzah Mohd Sarmin ◽  
Chyan Leong Ng ◽  
John J.L. Tiong ◽  
Wan M. Aizat ◽  
...  

BackgroundStreptomycesare well known for their capability to produce many bioactive secondary metabolites with medical and industrial importance. Here we report a novel bioactive phenazine compound, 6-((2-hydroxy-4-methoxyphenoxy) carbonyl) phenazine-1-carboxylic acid (HCPCA) extracted fromStreptomyces kebangsaanensis, an endophyte isolated from the ethnomedicinalPortulaca oleracea.MethodsThe HCPCA chemical structure was determined using nuclear magnetic resonance spectroscopy. We conducted whole genome sequencing for the identification of the gene cluster(s) believed to be responsible for phenazine biosynthesis in order to map its corresponding pathway, in addition to bioinformatics analysis to assess the potential ofS. kebangsaanensisin producing other useful secondary metabolites.ResultsTheS. kebangsaanensisgenome comprises an 8,328,719 bp linear chromosome with high GC content (71.35%) consisting of 12 rRNA operons, 81 tRNA, and 7,558 protein coding genes. We identified 24 gene clusters involved in polyketide, nonribosomal peptide, terpene, bacteriocin, and siderophore biosynthesis, as well as a gene cluster predicted to be responsible for phenazine biosynthesis.DiscussionThe HCPCA phenazine structure was hypothesized to derive from the combination of two biosynthetic pathways, phenazine-1,6-dicarboxylic acid and 4-methoxybenzene-1,2-diol, originated from the shikimic acid pathway. The identification of a biosynthesis pathway gene cluster for phenazine antibiotics might facilitate future genetic engineering design of new synthetic phenazine antibiotics. Additionally, these findings confirm the potential ofS. kebangsaanensisfor producing various antibiotics and secondary metabolites.


2018 ◽  
Vol 4 (4) ◽  
Author(s):  
Sergi Herve Akone ◽  
Cong-Dat Pham ◽  
Huiqin Chen ◽  
Antonius R. B. Ola ◽  
Fidele Ntie-Kang ◽  
...  

Abstract Fungi and bacteria are encountered in many habitats where they live in complex communities interacting with one another mainly by producing secondary metabolites, which are organic compounds that are not directly involved in the normal growth, development, or reproduction of the organism. These organisms appear as a promising source for the discovery of novel bioactive natural products that may find their application in medicine. However, the production of secondary metabolites by those organisms when cultured axenically is limited as only a subset of biosynthetic genes is expressed under standard laboratory conditions leading to the search of new methods for the activation of the silent genes including epigenetic modification and co-cultivation. Biosynthetic gene clusters which produce secondary metabolites are known to be present in a heterochromatin state in which the transcription of constitutive genes is usually regulated by epigenetic modification including DNA methylation and histone deacetylation. Therefore, small-molecule epigenetic modifiers which promote changes in the structure of chromatin could control the expression of silent genes and may be rationally employed for the discovery of novel bioactive compounds. Co-cultivation, which is also known as mixed-fermentation, usually implies two or more microorganisms in the same medium in which the resulting competition is known to enhance the production of constitutively present compounds and/or to lead to the induction of cryptic metabolites that were not detected in axenic cultures of the considered axenic microorganism. Genomic strategies could help to identify biosynthetic gene clusters in fungal genomes and link them to their products by the means of novel algorithms as well as integrative pan-genomic approaches. Despite that all these techniques are still in their infancy, they appear as promising sources for the discovery of new bioactive compounds. This chapter presents recent ecological techniques for the discovery of new secondary metabolites that might find application in medicine.


Author(s):  
Kai Huang ◽  
Bo Zhang ◽  
Yu Chen ◽  
Zhi-Qiang Liu ◽  
Yu-Guo Zheng

Antibiotics play an important role in human health. Most antibiotics are derived from microbial secondary metabolites. Amphotericin is a polyene macrolide antibiotic synthesized by Streptomyces nodosus. S. nodosus ZJB2016050 with high-yield amphotericin B (AmB) was obtained by traditional mutagenesis using S. nodosus ATCC14899 as the original strain. The differences in the characterization of the two strains were found in color, mycelium morphology, and AmB yield. Subsequent comparative transcriptome explained the yield differences between the two strains. Pathways including the carbohydrate metabolic pathway and the secondary product synthesis pathway were targeted. The upregulation of glucokinase, phosphoglycerate mutase, and pyruvate dehydrogenase accelerates the consumption of glucose and has great effects on the accumulation of precursors. One of the competitive secondary metabolites of the polyketone synthetase (PKS) II type sapromomycin analog synthesis gene cluster was downregulated, which competes for malonyl-CoA. Five PKS modules (except for the first module amphA) of the amphotericin synthetic gene cluster in the high-yielding strain were downregulated, which resulted in the total amphotericin A (AmA) and AmB of S. nodosus ZJB2016050 being less than that of the wild-type S. nodosus ATCC14899. Combined with gene differential expression in the pentose phosphate pathway and the reaction mechanism of the ER5 domain, the reason that S. nodosus ZJB2016050 preferred to synthesize AmB was probably related to intracellular reduction.


2018 ◽  
Vol 1 (1) ◽  
Author(s):  
Hooi-Leng Ser ◽  
Wai-Fong Yin ◽  
Kok-Gan Chan ◽  
Nurul-Syakima Ab Mutalib ◽  
Learn-Han Lee

Novosphingobium malaysiense strain MUSC 273T is a recently identified Gram-negative, aerobic alpha-proteobacterium. The strain was isolated from intertidal soil with strong catalase activity. The genome sequence comprises 5,027,021 bp, with 50 tRNA and 3 rRNA genes. Further analysis identified presence of secondary metabolite gene clusters within genome of MUSC 273T. Knowledge of the genomic features of the strain may allow further biotechnological exploitation, particularly for production of secondary metabolites as well as production of industrially important enzymes


eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Zachary Charlop-Powers ◽  
Jeremy G Owen ◽  
Boojala Vijay B Reddy ◽  
Melinda A Ternei ◽  
Denise O Guimarães ◽  
...  

Recent bacterial (meta)genome sequencing efforts suggest the existence of an enormous untapped reservoir of natural-product-encoding biosynthetic gene clusters in the environment. Here we use the pyro-sequencing of PCR amplicons derived from both nonribosomal peptide adenylation domains and polyketide ketosynthase domains to compare biosynthetic diversity in soil microbiomes from around the globe. We see large differences in domain populations from all except the most proximal and biome-similar samples, suggesting that most microbiomes will encode largely distinct collections of bacterial secondary metabolites. Our data indicate a correlation between two factors, geographic distance and biome-type, and the biosynthetic diversity found in soil environments. By assigning reads to known gene clusters we identify hotspots of biomedically relevant biosynthetic diversity. These observations not only provide new insights into the natural world, they also provide a road map for guiding future natural products discovery efforts.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 248
Author(s):  
Chang Ha Park ◽  
Hyeon Ji Yeo ◽  
Ye Jin Kim ◽  
Bao Van Nguyen ◽  
Ye Eun Park ◽  
...  

This study aimed to elucidate the variations in primary and secondary metabolites during Lycorisradiata flower development using high performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOFMS). The result showed that seven carotenoids, seven phenolic acids, three anthocyanins, and galantamine were identified in the L. radiata flowers. Most secondary metabolite levels gradually decreased according to the flower developmental stages. A total of 51 metabolites, including amines, sugars, sugar intermediates, sugar alcohols, amino acids, organic acids, phenolic acids, and tricarboxylic acid (TCA) cycle intermediates, were identified and quantified using GC-TOFMS. Among the hydrophilic compounds, most amino acids increased during flower development; in contrast, TCA cycle intermediates and sugars decreased. In particular, glutamine, asparagine, glutamic acid, and aspartic acid, which represent the main inter- and intracellular nitrogen carriers, were positively correlated with the other amino acids and were negatively correlated with the TCA cycle intermediates. Furthermore, quantitation data of the 51 hydrophilic compounds were subjected to partial least-squares discriminant analyses (PLS-DA) to assess significant differences in the metabolites of L. radiata flowers from stages 1 to 4. Therefore, this study will serve as the foundation for a biochemical approach to understand both primary and secondary metabolism in L. radiata flower development.


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