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1.
Mol Biol Evol ; 40(8)2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37494294

RESUMO

The roles of DNA methylation in invertebrates are poorly characterized, and critical data are missing for the phylum Annelida. We fill this knowledge gap by conducting the first genome-wide survey of DNA methylation in the deep-sea polychaetes dominant in deep-sea vents and seeps: Paraescarpia echinospica, Ridgeia piscesae, and Paralvinella palmiformis. DNA methylation calls were inferred from Oxford Nanopore sequencing after assembling high-quality genomes of these animals. The genomes of these worms encode all the key enzymes of the DNA methylation metabolism and possess a mosaic methylome similar to that of other invertebrates. Transcriptomic data of these polychaetes support the hypotheses that gene body methylation strengthens the expression of housekeeping genes and that promoter methylation acts as a silencing mechanism but not the hypothesis that DNA methylation suppresses the activity of transposable elements. The conserved epigenetic profiles of genes responsible for maintaining homeostasis under extreme hydrostatic pressure suggest DNA methylation plays an important adaptive role in these worms.


Assuntos
Anelídeos , Poliquetos , Animais , Epigenoma , Poliquetos/genética , Poliquetos/metabolismo , Perfilação da Expressão Gênica , Genoma , Metilação de DNA
2.
Mol Ecol ; 33(1): e17200, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37985390

RESUMO

Information on genetic divergence and migration patterns of vent- and seep-endemic macrobenthos can help delimit biogeographical provinces and provide scientific guidelines for deep-sea conservation under the growing threats of anthropogenic disturbances. Nevertheless, related studies are still scarce, impeding the informed conservation of these hotspots of deep-sea biodiversity. To bridge this knowledge gap, we conducted a population connectivity study on the galatheoid squat lobster Shinkaia crosnieri - a deep-sea foundation species widely distributed in vent and seep ecosystems in the Northwest Pacific. With the application of an interdisciplinary methodology involving population genomics and oceanographic approaches, we unveiled two semi-isolated lineages of S. crosnieri with limited and asymmetrical gene flow potentially shaped by the geographic settings, habitat types, and ocean currents - one comprising vent populations in the Okinawa Trough, with those inhabiting the southern trough area likely serving as the source; the other being the Jiaolong (JR) seep population in the South China Sea. The latter might have recently experienced a pronounced demographic contraction and exhibited genetic introgression from the Okinawa Trough lineage, potentially mediated by the intrusion of the North Pacific Intermediate Water. We then compared the biogeographic patterns between S. crosnieri and two other representative and co-occurring vent- and seep-endemic species using published data. Based on their biogeographical subdivisions and source-sink dynamics, we highlighted the southern Okinawa Trough vents and the JR seep warrant imperative conservation efforts to sustain the deep-sea biodiversity in the Northwest Pacific.


Assuntos
Ecossistema , Fontes Hidrotermais , Filogenia , Biodiversidade , Deriva Genética , China
3.
J Nat Prod ; 87(4): 876-883, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38377956

RESUMO

Cytochrome P450-modified bacterial terpenoids remain in a vast chemical space to be explored. In the present study, we conducted global genome mining of 223,829 bacterial genomes and identified 2892 bacterial terpenoid biosynthetic gene clusters (BGCs) with cytochrome P450 genes. Among these, we selected 562 with multiple P450 enzymes, which were further clustered as 355 gene cluster families by sequence similarity analysis. We then chose lev, a BGC from Streptomyces levis MCCC1A01616, for heterologous expression and discovered four new α-amorphene-type sesquiterpenoids, levinoids A-D (1-4). The structures and absolute configurations of these four new compounds were determined by employing extensive NMR analysis, NMR chemical shift calculations with DP4+, and ECD calculations. Furthermore, levinoid C (3) exhibited a moderate level of neuroprotective activity (EC50 = 21 µM) in the glutamate-induced excitotoxicity cell model. Our findings highlight the untapped chemical diversity of P450-modified bacterial terpenoids, opening new avenues for further exploration and discovery.


Assuntos
Sistema Enzimático do Citocromo P-450 , Sesquiterpenos , Streptomyces , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sistema Enzimático do Citocromo P-450/metabolismo , Streptomyces/química , Streptomyces/genética , Estrutura Molecular , Genoma Bacteriano , Família Multigênica , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química
4.
Proc Biol Sci ; 290(2009): 20231563, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37876192

RESUMO

Members of the phylum Cnidaria include sea anemones, corals and jellyfish, and have successfully colonized both marine and freshwater habitats throughout the world. The understanding of how cnidarians adapt to extreme environments such as the dark, high-pressure deep-sea habitat has been hindered by the lack of genomic information. Here, we report the first chromosome-level deep-sea cnidarian genome, of the anemone Actinernus sp., which was 1.39 Gbp in length and contained 44 970 gene models including 14 806 tRNA genes and 30 164 protein-coding genes. Analyses of homeobox genes revealed the longest chromosome hosts a mega-array of Hox cluster, HoxL, NK cluster and NKL homeobox genes; until now, such an array has only been hypothesized to have existed in ancient ancestral genomes. In addition to this striking arrangement of homeobox genes, analyses of microRNAs revealed cnidarian-specific complements that are distinctive for nested clades of these animals, presumably reflecting the progressive evolution of the gene regulatory networks in which they are embedded. Also, compared with other sea anemones, circadian rhythm genes were lost in Actinernus sp., which likely reflects adaptation to living in the dark. This high-quality genome of a deep-sea cnidarian thus reveals some of the likely molecular adaptations of this ecologically important group of metazoans to the extreme deep-sea environment. It also deepens our understanding of the evolution of genome content and organization of animals in general and cnidarians in particular, specifically from the viewpoint of key developmental control genes like the homeobox-encoding genes, where we find an array of genes that until now has only been hypothesized to have existed in the ancient ancestor that pre-dated both the cnidarians and bilaterians.


Assuntos
Cnidários , Anêmonas-do-Mar , Animais , Anêmonas-do-Mar/genética , Genes Homeobox , Filogenia , Evolução Molecular , Família Multigênica
5.
Mol Ecol ; 32(18): 5071-5088, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37584177

RESUMO

Acquisition of new genes often results in the emergence of novel functions and is a key step in lineage-specific adaptation. As a group of sessile crustaceans, barnacles establish permanent attachment through initial cement secretion at the larval phase followed by continuous cement secretion in juveniles and adults. However, the origins and evolution of barnacle larval and adult cement proteins remain poorly understood. By performing microdissection of larval cement glands, transcriptome and shotgun proteomics and immunohistochemistry validation, we identified 30 larval and 27 adult cement proteins of the epibiotic turtle barnacle Chelonibia testudinaria, of which the majority are stage- and barnacle-specific. While only two proteins, SIPC and CP100K, were expressed in both larvae and adults, detection of protease inhibitors and the cross-linking enzyme lysyl oxidase paralogs in larvae and adult cement. Other barnacle-specific cement proteins such as CP100k and CP52k likely share a common origin dating back at least to the divergence of Rhizocephala and Thoracica. Different CP52k paralogues could be detected in larval and adult cement, suggesting stage-specific cement proteins may arise from duplication followed by changes in expression timing of the duplicates. Interestingly, the biochemical properties of larval- and adult-specific CP52k paralogues exhibited remarkable differences. We conclude that barnacle larval and adult cement systems evolved independently, and both emerged from co-option of existing genes and de novo formation, duplication and functional divergence of lineage-specific cement protein genes. Our findings provide important insights into the evolutionary mechanisms of bioadhesives in sessile marine invertebrates.


Assuntos
Thoracica , Animais , Thoracica/genética , Thoracica/metabolismo , Proteínas/genética , Larva/genética , Larva/metabolismo , Transcriptoma/genética
6.
Mol Ecol ; 32(5): 1098-1116, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36528869

RESUMO

Thermal priming of reef corals can enhance their heat tolerance; however, the legacy effects of heat stress during parental brooding on larval resilience remain understudied. This study investigated whether preconditioning adult coral Pocillopora damicornis to high temperatures (29°C and 32°C) could better prepare their larvae for heat stress. Results showed that heat-acclimated adults brooded larvae with reduced symbiont density and shifted thermal performance curves. Reciprocal transplant experiments demonstrated higher bleaching resistance and better photosynthetic and autotrophic performance in heat-exposed larvae from acclimated adults compared to unacclimated adults. RNA-seq revealed strong cellular stress responses in larvae from heat-acclimated adults that could have been effective in rescuing host cells from stress, as evidenced by the widespread upregulation of genes involved in cell cycle and mitosis. For symbionts, a molecular coordination between light harvesting, photoprotection and carbon fixation was detected in larvae from heat-acclimated adults, which may help optimize photosynthetic activity and yield under high temperature. Furthermore, heat acclimation led to opposing regulations of symbiont catabolic and anabolic pathways and favoured nutrient translocation to the host and thus a functional symbiosis. Notwithstanding, the improved heat tolerance was paralleled by reduced light-enhanced dark respiration, indicating metabolic depression for energy saving. Our findings suggest that adult heat acclimation can rapidly shift thermal tolerance of brooded coral larvae and provide integrated physiological and molecular evidence for this adaptive plasticity, which could increase climate resilience. However, the metabolic depression may be maladaptive for long-term organismal performance, highlighting the importance of curbing carbon emissions to better protect corals.


Assuntos
Antozoários , Termotolerância , Animais , Antozoários/genética , Recifes de Corais , Larva , Termotolerância/genética , Aclimatação , Simbiose
7.
Mol Ecol ; 32(24): 6796-6808, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37888909

RESUMO

The dissolution of anthropogenic carbon dioxide (CO2 ) in seawater has altered its carbonate chemistry in the process of ocean acidification (OA). OA affects the viability of marine species. In particular, calcifying organisms and their early planktonic larval stages are considered vulnerable. These organisms often utilize energy reserves for metabolism rather than growth and calcification as supported by bulk RNA-sequencing (RNA-seq) experiments. Yet, transcriptomic profiling of a bulk sample reflects the average gene expression of the population, neglecting the variations between individuals, which forms the basis for natural selection. Here, we used single-embryo RNA-seq on larval sea urchin Heliocidaris crassispina, which is a commercially and ecologically valuable species in East Asia, to document gene expression changes to OA at an individual and family level. Three paternal half-sibs groups were fertilized and exposed to 3 pH conditions (ambient pH 8.0, 7.7 and 7.4) for 12 h prior to sequencing and oxygen consumption assay. The resulting transcriptomic profile of all embryos can be distinguished into four clusters, with differences in gene expressions that govern biomineralization, cell differentiation and patterning, as well as metabolism. While these responses were influenced by pH conditions, the male identities also had an effect. Specifically, a regression model and goodness of fit tests indicated a significant interaction between sire and pH on the probability of embryo membership in different clusters of gene expression. The single-embryo RNA-seq approach is promising in climate stressor research because not only does it highlight potential impacts before phenotypic changes were observed, but it also highlights variations between individuals and lineages, thus enabling a better determination of evolutionary potential.


Assuntos
Ouriços-do-Mar , Água do Mar , Humanos , Animais , Masculino , Água do Mar/química , Concentração de Íons de Hidrogênio , Ouriços-do-Mar/genética , Perfilação da Expressão Gênica , Larva/fisiologia , Transcriptoma/genética , Dióxido de Carbono/química , Oceanos e Mares
8.
Nat Chem Biol ; 17(5): 576-584, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33664521

RESUMO

Cariogenic Streptococcus mutans is known as a predominant etiological agent of dental caries due to its exceptional capacity to form biofilms. From strains of S. mutans isolated from dental plaque, we discovered, in the present study, a polyketide/nonribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability. We then identified the muf-associated bioactive product, mutanofactin-697, which contains a new molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies revealed that mutanofactin-697 binds to S. mutans cells and also extracellular DNA, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation. Our findings provided an example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the importance of secondary metabolism in mediating critical processes related to the development of dental caries.


Assuntos
Biofilmes/efeitos dos fármacos , Fatores Biológicos/biossíntese , Genes Bacterianos , Metabolismo Secundário/genética , Streptococcus mutans/metabolismo , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Fatores Biológicos/isolamento & purificação , Fatores Biológicos/farmacologia , Biologia Computacional/métodos , DNA/genética , DNA/metabolismo , Cárie Dentária/microbiologia , Cárie Dentária/patologia , Regulação Bacteriana da Expressão Gênica , Humanos , Interações Hidrofóbicas e Hidrofílicas , Família Multigênica , Biossíntese de Peptídeos Independentes de Ácido Nucleico , Ligação Proteica , Streptococcus mutans/genética , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/patogenicidade
9.
Environ Sci Technol ; 57(26): 9515-9525, 2023 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-37338959

RESUMO

Marine biofilms are multispecies microbial communities on surfaces that are crucial to the marine environment. They cause marine corrosion, biofouling, and transmission of marine pathogens and thus pose a great threat to public health and the maritime industry. To control marine biofilms, effective and environmentally friendly antibiofilm compounds are highly needed. Elasnin is a potent antibiofilm compound that exhibits high efficiency in inhibiting marine biofilms and biofouling, but its mode of action remains unclear. In the present study, multiomic analysis combined with quorum-sensing assays and in silico study revealed that elasnin acted as a signaling molecule in the microbial community. Elasnin promoted the growth of dominant species in the biofilm but deprived their ability of sensing and responding to environmental changes by disturbing their regulations of the two-component system, i.e., the ATP-binding cassette transport system and the bacterial secretion system. Consequently, biofilm maturation and subsequent biofouler settlement were inhibited. Elasnin also exhibited higher antibiofilm efficiency than dichlorooctylisothiazolinone and had low toxicity potential on the embryos and adults of marine medaka fish. Overall, this study provided molecular and ecological insights into elasnin's mode of action, highlighting its application potential in controlling marine biofilms and the feasibility and advantages of using signal molecules to develop eco-friendly technologies.


Assuntos
Biofilmes , Incrustação Biológica , Animais , Percepção de Quorum , Incrustação Biológica/prevenção & controle , Pironas/farmacologia
10.
Nucleic Acids Res ; 49(10): 5881-5890, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34048588

RESUMO

The hexanucleotide repeat expansion, GGGGCC (G4C2), within the first intron of the C9orf72 gene is known to be the most common genetic cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The G4C2 repeat expansions, either DNA or RNA, are able to form G-quadruplexes which induce toxicity leading to ALS/FTD. Herein, we report a novel crystal structure of d(G4C2)2 that self-associates to form an eight-layer parallel tetrameric G-quadruplex. Two d(G4C2)2 associate together as a parallel dimeric G-quadruplex which folds into a tetramer via 5'-to-5' arrangements. Each dimer consists of four G-tetrads connected by two CC propeller loops. Especially, the 3'-end cytosines protrude out and form C·C+•C·C+/ C·C•C·C+ quadruple base pair or C•C·C+ triple base pair stacking on the dimeric block. Our work sheds light on the G-quadruplexes adopted by d(G4C2) and yields the invaluable structural details for the development of small molecules to tackle neurodegenerative diseases, ALS and FTD.


Assuntos
Esclerose Lateral Amiotrófica/genética , Proteína C9orf72/química , Proteína C9orf72/genética , Expansão das Repetições de DNA , DNA/química , Demência Frontotemporal/genética , Quadruplex G , Sequências Repetitivas de Ácido Nucleico/genética , Dicroísmo Circular , Citosina/química , Dimerização , Humanos , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Proteica
11.
J Environ Manage ; 331: 117238, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36681031

RESUMO

The production of shale gas in China has repercussions for the global energy landscape and carbon neutrality. However, limited and threatened water resources may hinder the expansion of shale-derived natural gas, one of China's most promising development prospects. Coupling historical trends with policy guidance, we project that baseline water stress will intensify in two-thirds of China's provinces in the next decade. By 2035, annual water use for shale gas hydraulic fracturing activities is likely to increase to 16-35 million m3, with 13.8-23.7 million m3 of wastewater produced annually to extract 38-48 billion m3 of gas from ∼4800 shale gas wells. Analysis suggests that this projection is based on previously underestimated geological constraints (e.g., deep continental facies) in shale gas development in China. Nevertheless, forecasts suggest that the water footprint of shale development will become impossible to ignore, particularly in drought-stricken areas, indicating the potential risk of competition for water among shale development, domestic use, food production, and ecological protection. Meanwhile, the annual wastewater management market will increase to $0.2 billion by 2035. Our study suggests a critical need to direct attention to the (shale) energy-water nexus and develop multi-pronged policies to facilitate China's transition to carbon neutrality.


Assuntos
Gás Natural , Águas Residuárias , Carbono , Campos de Petróleo e Gás , China , Minerais
12.
Mol Biol Evol ; 38(12): 5640-5654, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34534352

RESUMO

Hydrothermal vents and hydrocarbon seeps in the deep ocean are rare oases fueled by chemosynthesis. Biological communities inhabiting these ecosystems are often distributed in widely separated habitats, raising intriguing questions on how these organisms achieve connectivity and whether habitat types facilitate intraspecific divergence. The deep-sea patellogastropod limpet Bathyacmaea nipponica that colonizes both vents and seeps across ∼2,400 km in the Northwest Pacific is a feasible model to answer these questions. We analyzed 123 individuals from four vents and three seeps using a comprehensive method incorporating population genomics and physical ocean modeling. Genome survey sequencing and genotyping-by-sequencing resulted in 9,838 single-nucleotide polymorphisms for population genomic analyses. Genetic divergence and demographic analyses revealed four habitat-linked (i.e., three seep and one vent) genetic groups, with the vent genetic group established via the opportunistic invasion of a few limpet larvae from a nearby seep genetic group. TreeMix analysis uncovered three historical seep-to-vent migration events. ADMIXTURE and divMigrate analyses elucidated weak contemporary gene flow from a seep genetic group to the vent genetic group. Physical ocean modeling underlined the potential roles of seafloor topography and ocean currents in shaping the genetic connectivity, contemporary migration, and local hybridization of these deep-sea limpets. Our study highlighted the power of integrating genomic and oceanographic approaches in deciphering the demography and diversification of deep-sea organisms. Given the increasing anthropogenic activities (e.g., mining and gas hydrate extraction) affecting the deep ocean, our results have implications for the conservation of deep-sea biodiversity and establishment of marine protected areas.


Assuntos
Gastrópodes , Fluxo Gênico , Fontes Hidrotermais , Animais , Biodiversidade , Ecossistema , Gastrópodes/genética
13.
Mol Biol Evol ; 38(2): 502-518, 2021 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-32956455

RESUMO

Endosymbiosis with chemosynthetic bacteria has enabled many deep-sea invertebrates to thrive at hydrothermal vents and cold seeps, but most previous studies on this mutualism have focused on the bacteria only. Vesicomyid clams dominate global deep-sea chemosynthesis-based ecosystems. They differ from most deep-sea symbiotic animals in passing their symbionts from parent to offspring, enabling intricate coevolution between the host and the symbiont. Here, we sequenced the genomes of the clam Archivesica marissinica (Bivalvia: Vesicomyidae) and its bacterial symbiont to understand the genomic/metabolic integration behind this symbiosis. At 1.52 Gb, the clam genome encodes 28 genes horizontally transferred from bacteria, a large number of pseudogenes and transposable elements whose massive expansion corresponded to the timing of the rise and subsequent divergence of symbiont-bearing vesicomyids. The genome exhibits gene family expansion in cellular processes that likely facilitate chemoautotrophy, including gas delivery to support energy and carbon production, metabolite exchange with the symbiont, and regulation of the bacteriocyte population. Contraction in cellulase genes is likely adaptive to the shift from phytoplankton-derived to bacteria-based food. It also shows contraction in bacterial recognition gene families, indicative of suppressed immune response to the endosymbiont. The gammaproteobacterium endosymbiont has a reduced genome of 1.03 Mb but retains complete pathways for sulfur oxidation, carbon fixation, and biosynthesis of 20 common amino acids, indicating the host's high dependence on the symbiont for nutrition. Overall, the host-symbiont genomes show not only tight metabolic complementarity but also distinct signatures of coevolution allowing the vesicomyids to thrive in chemosynthesis-based ecosystems.


Assuntos
Bivalves/microbiologia , Transferência Genética Horizontal , Genoma , Fontes Hidrotermais/microbiologia , Simbiose , Sequência de Aminoácidos , Animais , Bivalves/fisiologia , Hemoglobinas/química , Hemoglobinas/genética , Sistema Imunitário , Filogenia , Piscirickettsiaceae/genética
14.
Mol Biol Evol ; 38(10): 4116-4134, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34255082

RESUMO

Vestimentiferan tubeworms are iconic animals that present as large habitat-forming chitinized tube bushes in deep-sea chemosynthetic ecosystems. They are gutless and depend entirely on their endosymbiotic sulfide-oxidizing chemoautotrophic bacteria for nutrition. Information on the genomes of several siboglinid endosymbionts has improved our understanding of their nutritional supplies. However, the interactions between tubeworms and their endosymbionts remain largely unclear due to a paucity of host genomes. Here, we report the chromosome-level genome of the vestimentiferan tubeworm Paraescarpia echinospica. We found that the genome has been remodeled to facilitate symbiosis through the expansion of gene families related to substrate transfer and innate immunity, suppression of apoptosis, regulation of lysosomal digestion, and protection against oxidative stress. Furthermore, the genome encodes a programmed cell death pathway that potentially controls the endosymbiont population. Our integrated genomic, transcriptomic, and proteomic analyses uncovered matrix proteins required for the formation of the chitinous tube and revealed gene family expansion and co-option as evolutionary mechanisms driving the acquisition of this unique supporting structure for deep-sea tubeworms. Overall, our study provides novel insights into the host's support system that has enabled tubeworms to establish symbiosis, thrive in deep-sea hot vents and cold seeps, and produce the unique chitinous tubes in the deep sea.


Assuntos
Fontes Hidrotermais , Simbiose , Animais , Quitina , Ecossistema , Genômica , Fontes Hidrotermais/microbiologia , Proteômica , Simbiose/genética
15.
Nat Prod Rep ; 39(5): 991-1014, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35288725

RESUMO

Covering: up to 2021Colibactin(s), a group of secondary metabolites produced by the pks island (clb cluster) of Escherichia coli, shows genotoxicity relevant to colorectal cancer and thus significantly affects human health. Over the last 15 years, substantial efforts have been exerted to reveal the molecular structure of colibactin, but progress is slow owing to its instability, low titer, and elusive and complex biosynthesis logic. Fortunately, benefiting from the discovery of the prodrug mechanism, over 40 precursors of colibactin have been reported. Some key biosynthesis genes located on the pks island have also been characterised. Using an integrated bioinformatics, metabolomics, and chemical synthesis approach, researchers have recently characterised the structure and possible biosynthesis processes of colibactin, thereby providing new insights into the unique biosynthesis logic and the underlying mechanism of the biological activity of colibactin. Early developments in the study of colibactin have been summarised in several previous reviews covering various study periods, whereas the two most recent reviews have focused primarily on the chemical synthesis of colibactin. The present review aims to provide an update on the biosynthesis and bioactivities of colibactin.


Assuntos
Mutagênicos , Policetídeos , Escherichia coli/genética , Escherichia coli/metabolismo , Humanos , Mutagênicos/metabolismo , Peptídeos/química , Policetídeos/metabolismo
16.
Environ Microbiol ; 24(9): 4108-4123, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35416402

RESUMO

The consequences of soils exposed to hydraulic fracturing (HF) return fluid, often collectively termed flowback and produced water (FPW), are poorly understood, even though soils are a common receptor of FPW spills. Here, we investigate the impacts on soil microbiota exposed to FPW collected from the Montney Formation of western Canada. We measured soil respiration, microbial community structure and functional potentials under FPW exposure across a range of concentrations, exposure time and soil types (luvisol and chernozem). We find that soil type governs microbial community response upon FPW exposure. Within each soil, FPW exposure led to reduced biotic soil respiration, and shifted microbial community structure and functional potentials. We detect substantially higher species richness and more unique functional genes in FPW-exposed soils than in FPW-unexposed soils, with metagenome-assembled genomes (e.g. Marinobacter persicus) from luvisol soil exposed to concentrated FPW being most similar to genomes from HF/FPW sites. Our data demonstrate the complex impacts of microbial communities following FPW exposure and highlight the site-specific effects in evaluation of spills and agricultural reuse of FPW on the normal soil functions.


Assuntos
Fraturamento Hidráulico , Microbiota , Poluentes Químicos da Água , Microbiota/genética , Respiração , Solo , Microbiologia do Solo , Águas Residuárias/química , Água , Poluentes Químicos da Água/análise
17.
J Nat Prod ; 85(7): 1751-1762, 2022 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-35703501

RESUMO

Bacteria in marine biofilms are a rich reservoir of natural products. To facilitate novel secondary metabolite discovery, we investigated the metabolic profile of a marine biofilm-derived Bacillus sp. B19-2 by combining bioinformatics and LC-UV-MS analyses. After dereplication and purification of putatively unknown compounds, a new family of compounds 1-8 was uncovered and named bathiapeptides. Structural elucidation using NMR, HRESIMS, ozonolysis, advanced Marfey's analysis, and X-ray diffraction revealed that bathiapeptides are polypeptides that contain a rare polythiazole moiety. These compounds exhibited strong cytotoxicity against Hep G2, HeLa, MCF-7, and MGC-803 cell lines, and the lowest IC50 value was 0.5 µM. An iterative biosynthesis logic in bathiapeptides' biosynthesis was proposed based on the identified chemical structures and putative gene cluster analysis.


Assuntos
Bacillus , Produtos Biológicos , Bacillus/metabolismo , Biofilmes , Produtos Biológicos/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Peptídeos/metabolismo
18.
Nucleic Acids Res ; 48(19): 11146-11161, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-32986843

RESUMO

The six-subunit origin recognition complex (ORC), a DNA replication initiator, defines the localization of the origins of replication in eukaryotes. The Orc6 subunit is the smallest and the least conserved among ORC subunits. It is required for DNA replication and essential for viability in all species. Orc6 in metazoans carries a structural homology with transcription factor TFIIB and can bind DNA on its own. Here, we report a solution structure of the full-length human Orc6 (HsOrc6) alone and in a complex with DNA. We further showed that human Orc6 is composed of three independent domains: N-terminal, middle and C-terminal (HsOrc6-N, HsOrc6-M and HsOrc6-C). We also identified a distinct DNA-binding domain of human Orc6, named as HsOrc6-DBD. The detailed analysis of the structure revealed novel amino acid clusters important for the interaction with DNA. Alterations of these amino acids abolish DNA-binding ability of Orc6 and result in reduced levels of DNA replication. We propose that Orc6 is a DNA-binding subunit of human/metazoan ORC and may play roles in targeting, positioning and assembling the functional ORC at the origins.


Assuntos
Replicação do DNA , DNA/metabolismo , Complexo de Reconhecimento de Origem/metabolismo , Origem de Replicação , Humanos , Ligação Proteica , Domínios Proteicos
19.
Mar Drugs ; 20(6)2022 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-35736201

RESUMO

Large-scale genome-mining analyses have identified an enormous number of cryptic biosynthetic gene clusters (BGCs) as a great source of novel bioactive natural products. Given the sheer number of natural product (NP) candidates, effective strategies and computational methods are keys to choosing appropriate BGCs for further NP characterization and production. This review discusses genomics-based approaches for prioritizing candidate BGCs extracted from large-scale genomic data, by highlighting studies that have successfully produced compounds with high chemical novelty, novel biosynthesis pathway, and potent bioactivities. We group these studies based on their BGC-prioritization logics: detecting presence of resistance genes, use of phylogenomics analysis as a guide, and targeting for specific chemical structures. We also briefly comment on the different bioinformatics tools used in the field and examine practical considerations when employing a large-scale genome mining study.


Assuntos
Produtos Biológicos , Produtos Biológicos/metabolismo , Vias Biossintéticas/genética , Biologia Computacional/métodos , Genoma Bacteriano , Genômica , Família Multigênica
20.
Proteomics ; 21(19): e2100118, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34329538

RESUMO

No sunlight can reach the hadal trench, but some fishes dwelling there still have apparent eye morphology. However, whether they are capable of sensing light remains unknown. In this study, the eyes of the dominant hadal endemic snailfish Pseudoliparis swirei from the Mariana Trench were analyzed using liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). A total of 2088 proteins were identified in the eye proteome, most of which had at least one hit against public databases and could be mapped to 316 metabolic pathways. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways directly contributing to visual phototransduction were significantly enriched from the top 10% dominant proteins, implying abundant metabolic activities in the eye and it is still a functional visual organ. One rhodopsin was identified in the eye proteome, sequence analysis indicated that it might have an absorption maximum at ∼480 nm and be sensitive to dim blue light. In addition, proteins that might contribute to extreme environment adaptation, such as heat shock proteins and chaperonin-containing T-complex protein 1, were also highly expressed in the eye. Overall, these results provide insights into the molecular mechanism underlying the vision of hadal snailfish and provide a useful database for further research.


Assuntos
Proteômica , Espectrometria de Massas em Tandem , Aclimatação , Animais , Cromatografia Líquida , Peixes
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