secondary metabolite

次生代谢产物
  • 文章类型: Journal Article
    链霉菌属是次生代谢产物的有吸引力的来源,是抗生素和其他药物的主要来源。在这项研究中,基因组挖掘用于确定链霉菌的生物合成潜力。21So2-11分离自南极土壤。16SrRNA基因测序显示,该菌株与drozdowiczii链霉菌NBRC101007T最密切相关,相似度为98.02%。基于平均核苷酸同一性(ANI)和数字DNA-DNA杂交(dDDH)的基因组比较表明,菌株21So2-11代表链霉菌属的新物种。除了大量与环境适应和生态功能相关的基因,共有28个推定的生物合成基因簇(BGC)负责已知和/或新的次级代谢产物的生物合成,包括萜烯,抗肽,聚酮化合物,非核糖体肽,RiPP和铁载体,在菌株21So2-11的基因组中检测到。此外,根据来自极地地区的47个链霉菌菌株的基因组,预计总共有1456个BGC有助于300多种次生代谢产物的生物合成。结果表明链霉菌的潜力。21So2-11用于生物活性次级代谢产物的生产,有助于了解细菌在寒冷的陆地环境中的适应性和生态功能。
    Streptomyces species are attractive sources of secondary metabolites that serve as major sources of antibiotics and other drugs. In this study, genome mining was used to determine the biosynthetic potential of Streptomyces sp. 21So2-11 isolated from Antarctic soil. 16S rRNA gene sequencing revealed that this strain is most closely related to Streptomyces drozdowiczii NBRC 101007T, with a similarity of 98.02%. Genome comparisons based on average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) showed that strain 21So2-11 represents a novel species of the genus Streptomyces. In addition to a large number of genes related to environmental adaptation and ecological function, a total of 28 putative biosynthetic gene clusters (BGCs) responsible for the biosynthesis of known and/or novel secondary metabolites, including terpenes, lantipeptides, polyketides, nonribosomal peptides, RiPPs and siderophores, were detected in the genome of strain 21So2-11. In addition, a total of 1456 BGCs were predicted to contribute to the biosynthesis of more than 300 secondary metabolites based on the genomes of 47 Streptomyces strains originating from polar regions. The results indicate the potential of Streptomyces sp. 21So2-11 for bioactive secondary metabolite production and are helpful for understanding bacterial adaptability and ecological function in cold terrestrial environments.
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  • 文章类型: Journal Article
    Clavatols由于其不同的结构而表现出广泛的生物活性。基因组挖掘策略从青霉菌中确定了一个A5cla簇。MYA5,来自北极植物Dryasoctopetala,负责克拉沃托的生物合成。七个克拉沃尔,包括一种名为penicophenoneF(1)的新克拉沃醇衍生物和六种已知的克拉沃醇(2-7),从青霉菌中分离。使用转录组挖掘策略的MYA5。通过全面的光谱分析阐明了这些结构。抗菌,醛糖还原酶抑制,对化合物1-7进行了铁载体产生能力测定。化合物1和2在10μM浓度下对ALR2酶表现出抑制作用,抑制率分别为75.3%和71.6%。分别。化合物6对金黄色葡萄球菌和大肠杆菌具有抗菌活性,MIC值分别为4.0μg/mL和4.0μg/mL,分别。此外,化合物1、5和6也显示出潜在的铁结合能力。
    Clavatols exhibit a wide range of biological activities due to their diverse structures. A genome mining strategy identified an A5cla cluster from Penicillium sp. MYA5, derived from the Arctic plant Dryas octopetala, is responsible for clavatol biosynthesis. Seven clavatols, including one new clavatol derivate named penicophenone F (1) and six known clavatols (2-7), were isolated from Penicillium sp. MYA5 using a transcriptome mining strategy. These structures were elucidated by comprehensive spectroscopic analysis. Antibacterial, aldose reductase inhibition, and siderophore-producing ability assays were conducted on compounds 1-7. Compounds 1 and 2 demonstrated inhibitory effects on the ALR2 enzyme with inhibition rates of 75.3% and 71.6% at a concentration of 10 μM, respectively. Compound 6 exhibited antibacterial activity against Staphylococcus aureus and Escherichia coli with MIC values of 4.0 μg/mL and 4.0 μg/mL, respectively. Additionally, compounds 1, 5, and 6 also showed potential iron-binding ability.
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  • 文章类型: Journal Article
    假镰刀菌引起小麦的破坏性冠病。天鹅绒蛋白家族是发育中的关键调节剂,毒力,和真菌的次生代谢。我们使用基因置换策略对FpVelB进行了功能分析。与野生型相比,FpVelB的缺失降低了径向生长并增强了分生孢子的产生。此外,FpVelB通过多种机制调节真菌对非生物胁迫的应答。重要的是,小麦茎基部和头部的FpVelB缺失后,毒力降低。全基因组基因表达谱显示,FpVelB对基因的调控与上述表型相关的几个过程有关。包括“免疫”,\"膜\",和“抗氧化活性”,特别是关于次级代谢产物。最重要的是,我们证明,FpVelB通过影响脱氧雪腐镰刀菌烯醇的产生和调节PKS11基因的表达来调节病原体的毒力。总之,FpVelB对植物生长至关重要,无性发育,和非生物应激反应,并且对于通过假草的次级代谢产生完全毒力至关重要。
    Fusarium pseudograminearum causes destructive crown disease in wheat. The velvet protein family is a crucial regulator in development, virulence, and secondary metabolism of fungi. We conducted a functional analysis of FpVelB using a gene replacement strategy. The deletion of FpVelB decreased radial growth and enhanced conidial production compared to that of wild type. Furthermore, FpVelB modulates the fungal responses to abiotic stress through diverse mechanisms. Significantly, virulence decreased after the deletion of FpVelB in both the stem base and head of wheat. Genome-wide gene expression profiling revealed that the regulation of genes by FpVelB is associated with several processes related to the aforementioned phenotype, including \"immune\", \"membrane\", and \"antioxidant activity\", particularly with regard to secondary metabolites. Most importantly, we demonstrated that FpVelB regulates pathogen virulence by influencing deoxynivalenol production and modulating the expression of the PKS11 gene. In conclusion, FpVelB is crucial for plant growth, asexual development, and abiotic stress response and is essential for full virulence via secondary metabolism in F. pseudograminearum.
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  • 文章类型: Journal Article
    ADP核糖基化因子(Arf)家族的鸟嘌呤核苷酸结合蛋白及其激活蛋白(Arf-GAP)对于多种生物过程至关重要。这里,两个同源Arf-GAP,Age1(AoAge1)和Age2(AoAge2),在广泛的线虫诱捕真菌Arthrobotrys寡孢子中被发现。我们的结果表明,AoAge1,尤其是AoAge2,在菌丝生长中起着至关重要的作用。孢子形成,圈闭生产,应激反应,线粒体活性,DNA损伤,内吞作用,活性氧的产生,和自噬。值得注意的是,转录组数据显示,大约62.7%的基因被AoAge2直接或间接调控,Aoage2缺失中失调的基因在代谢中富集,核糖体生物发生,次级代谢产物生物合成,和自噬。此外,与野生型菌株相比,Aoage2失活导致几种化合物的大幅减少。基于这些结果,提出了AoAge1和AoAge2的监管网络,并使用酵母双杂交测定法进行了验证。根据我们的发现,AoAge1和AoAge2对营养生长和菌丝体发育至关重要。具体来说,AoAge2是孢子形成和捕获形态发生所必需的。我们的结果表明AoAge1和AoAge2在菌丝体生长中的关键功能,不同的细胞过程,和致病性,深入了解Arf-GAP在线虫诱捕真菌中的功能和调控机制。
    Guanine nucleotide-binding proteins of the ADP ribosylation factor (Arf) family and their activating proteins (Arf-GAPs) are essential for diverse biological processes. Here, two homologous Arf-GAPs, Age1 (AoAge1) and Age2 (AoAge2), were identified in the widespread nematode-trapping fungus Arthrobotrys oligospora. Our results demonstrated that AoAge1, especially AoAge2, played crucial roles in mycelial growth, sporulation, trap production, stress response, mitochondrial activity, DNA damage, endocytosis, reactive oxygen species production, and autophagy. Notably, transcriptome data revealed that approximately 62.7% of the genes were directly or indirectly regulated by AoAge2, and dysregulated genes in Aoage2 deletion were enriched in metabolism, ribosome biogenesis, secondary metabolite biosynthesis, and autophagy. Furthermore, Aoage2 inactivation caused a substantial reduction in several compounds compared to the wild-type strain. Based on these results, a regulatory network for AoAge1 and AoAge2 was proposed and verified using a yeast two-hybrid assay. Based on our findings, AoAge1 and AoAge2 are essential for vegetative growth and mycelial development. Specifically, AoAge2 is required for sporulation and trapping morphogenesis. Our results demonstrated the critical functions of AoAge1 and AoAge2 in mycelial growth, diverse cellular processes, and pathogenicity, offering deep insights into the functions and regulatory mechanisms of Arf-GAPs in nematode-trapping fungi.
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  • 文章类型: Journal Article
    木霉属。可以增强植物对各种生物胁迫的抵抗力。然而,木霉增强植物对南方根结线虫抗性的基本机制,被称为根结线虫(RKN),还不清楚。这里,我们确定了一种可以有效抑制番茄(SolanumlycopersicumL.)中RKN侵染的木霉菌(T141)菌株。线虫的侵染导致根中活性氧(ROS)和丙二醛(MDA)的浓度增加,但预接种T141可显着降低氧化应激。ROS和MDA的减少伴随着抗氧化酶活性的增加以及类黄酮和酚类物质的积累。此外,基于裂根试验的分析表明,在RKN接种之前,在局部根部接种T141会增加植物激素茉莉酸(JA)的浓度以及远处根部JA合成和信号相关基因的转录本。基于UPLC-MS/MS的代谢组学分析在根划分试验中通过4对比较确定了1051种差异积累的代谢物(DAM),包括81种类黄酮。值得注意的是,在RKN和T141-RKN之间的比较中发现了180个DAM,而KEGG注释和富集分析表明,次级代谢途径,尤其是类黄酮的生物合成,在T141诱导的系统对RKN的抵抗中起关键作用。通过山奈酚的外源处理的体外实验进一步验证了上调的黄酮类化合物在RKN死亡率中的作用,橙皮苷和芦丁在J2期RKN上。我们的结果表明,T141通过系统地促进远根的次生代谢来诱导番茄植株对RKN的抗性的关键机制。
    Trichoderma spp. can enhance plant resistance against a wide range of biotic stressors. However, the fundamental mechanisms by which Trichoderma enhances plant resistance against Meloidogyne incognita, known as root-knot nematodes (RKNs), are still unclear. Here, we identified a strain of Trichoderma asperellum (T141) that could effectively suppress RKN infestation in tomato (Solanum lycopersicum L.). Nematode infestation led to an increase in the concentrations of reactive oxygen species (ROS) and malondialdehyde (MDA) in roots but pre-inoculation with T141 significantly decreased oxidative stress. The reduction in ROS and MDA was accompanied by an increase in the activity of antioxidant enzymes and the accumulation of flavonoids and phenols. Moreover, split root test-based analysis showed that T141 inoculation in local roots before RKN inoculation increased the concentration of phytohormone jasmonate (JA) and the transcripts of JA synthesis and signaling-related genes in distant roots. UPLC-MS/MS-based metabolomics analysis identified 1051 differentially accumulated metabolites (DAMs) across 4 pairwise comparisons in root division test, including 81 flavonoids. Notably, 180 DAMs were found in comparison between RKN and T141-RKN, whereas KEGG annotation and enrichment analysis showed that the secondary metabolic pathways, especially the flavonoid biosynthesis, played a key role in the T141-induced systemic resistance to RKNs. The role of up-regulated flavonoids in RKN mortality was further verified by in vitro experiments with the exogenous treatment of kaempferol, hesperidin and rutin on J2-stage RKNs. Our results revealed a critical mechanism by which T141 induced resistance of tomato plants against the RKNs by systemically promoting secondary metabolism in distant roots.
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  • 文章类型: Journal Article
    重金属铜(Cu)将不可避免地影响海洋大型藻类龙须菜(G。lemeaneiformis),这是中国海岸线上具有经济重要性的文化。在这项研究中,通过评估Cu胁迫后1d的生理指标并结合转录组和代谢组分析,揭示了Cu胁迫对龙须菜的解毒机制。我们的发现表明,25μMCu刺激ROS合成并导致花生四烯酸残基的酶促氧化。这个过程随后通过抑制光合作用阻碍了龙须菜的生长,氮代谢,蛋白质合成,等。ZIP和IRT转运蛋白促进了Cu离子进入藻类,呈现为Cu2+。此外,Cu外排转运蛋白HMA5和ABC家族转运蛋白上调以实现分隔以减轻毒性。结果表明,龙须菜提高了抗氧化酶超氧化物歧化酶和抗坏血酸-谷胱甘肽循环,以维持ROS稳态。此外,黄酮类等代谢物,3-O-甲基没食子酸,3-羟基-4-酮-γ-胡萝卜素,与对照组相比,二十碳五烯酸上调,表明它们可能在应对铜胁迫中发挥作用。总之,这项研究提供了一个全面的了解解毒机制驱动的龙须菜对铜暴露的反应。
    Heavy metal copper (Cu) will inevitably impact the marine macroalgae Gracilariopsis lemaneiformis (G. lemaneiformis), which is a culture of economic importance along China\'s coastline. In this study, the detoxification mechanism of Cu stress on G. lemaneiformis was revealed by assessing physiological indicators in conjunction with transcriptome and metabolome analyses at 1 d after Cu stress. Our findings revealed that 25 μM Cu stimulated ROS synthesis and led to the enzymatic oxidation of arachidonic acid residues. This process subsequently impeded G. lemaneiformis growth by suppressing photosynthesis, nitrogen metabolism, protein synthesis, etc. The entry of Cu ions into the algae was facilitated by ZIPs and IRT transporters, presenting as Cu2+. Furthermore, there was an up-regulation of Cu efflux transporters HMA5 and ABC family transporters to achieve compartmentation to mitigate the toxicity. The results revealed that G. lemaneiformis elevated the antioxidant enzyme superoxide dismutase and ascorbate-glutathione cycle to maintain ROS homeostasis. Additionally, metabolites such as flavonoids, 3-O-methylgallic acid, 3-hydroxy-4-keto-gama-carotene, and eicosapentaenoic acid were up-regulated compared with the control, indicating that they might play roles in response to Cu stress. In summary, this study offers a comprehensive insight into the detoxification mechanisms driving the responses of G. lemaneiformis to Cu exposure.
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  • 文章类型: Journal Article
    这项研究解决了对水体中氰基毒素污染的日益关注,强调这些毒素的多样性及其潜在的健康影响。蓝细菌,在水生环境中普遍存在,产生有毒的代谢物,引起人们对人类暴露和相关健康风险的关注,包括癌症风险的潜在增加。尽管现有的研究主要集中在众所周知的氰毒素上,最近的技术进步揭示了许多未知的氰基毒素,需要对多种毒素类别进行全面评估。为了加强氰毒素数据库,我们使用MassFrontier碎片数据预测软件,通过纳入二次碎片模式,优化了CyanoMetDB蓝藻次生代谢产物数据库.使用高分辨率质谱分析了上海不同地区的水样。随后,使用甲壳动物Thamnocalusplatyurus通过急性毒性测定法检查了水样中蓝细菌代谢物的毒性。暴露24小时后,水样的半致死浓度(LC50)范围为0.31mgL-1至1.78mgL-1(MC-LR当量浓度)。我们的发现揭示了蓝细菌代谢物的总浓度与毒性之间的关键相关性。这项研究的强大框架和见解强调了对水质管理采取包容性方法的必要性,强调不断努力完善检测方法,了解蓝藻水华对水生生态系统的更广泛生态影响。
    This study addresses the increasing concern regarding cyanotoxin contamination of water bodies, highlighting the diversity of these toxins and their potential health implications. Cyanobacteria, which are prevalent in aquatic environments, produce toxic metabolites, raising concerns regarding human exposure and associated health risks, including a potential increase in cancer risk. Although existing research has primarily focused on well-known cyanotoxins, recent technological advancements have revealed numerous unknown cyanotoxins, necessitating a comprehensive assessment of multiple toxin categories. To enhance the cyanotoxin databases, we optimized the CyanoMetDB cyanobacterial secondary metabolites database by incorporating secondary fragmentation patterns using the Mass Frontier fragmentation data prediction software. Water samples from diverse locations in Shanghai were analyzed using high-resolution mass spectrometry. Subsequently, the toxicity of cyanobacterial metabolites in the water samples was examined through acute toxicity assays using the crustacean Thamnocephalus platyurus. After 24 h of exposure, the semi-lethal concentrations (LC50) of the water samples ranged from 0.31 mg L-1 to 1.78 mg L-1 (MC-LR equivalent concentration). Our findings revealed a critical correlation between the overall concentration of cyanobacterial metabolites and toxicity. The robust framework and insights of this study underscore the need for an inclusive approach to water quality management, emphasizing continuous efforts to refine detection methods and comprehend the broader ecological impact of cyanobacterial blooms on aquatic ecosystems.
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  • 文章类型: Journal Article
    普遍的神经系统疾病,如阿尔茨海默病,帕金森病,随着社会年龄的增长,中风越来越成为全球负担。众所周知,神经元的变性和丢失是基本的基础过程,但是这些神经系统疾病仍然没有有效的治疗方法。近年来,大量的研究集中在天然产物的药理学和可行性,作为开发针对神经系统疾病的药物的新策略。牛樟芝已成为最有前途的候选人之一,据报道,其粗提物和一些活性代谢产物在细胞和分子水平上发挥各种药理活性,缓解神经系统症状。这篇综述强调了樟芝对抗神经系统疾病的当前证据,包括安全评估,新陈代谢,血脑屏障穿透,神经保护活动,以及调节肠道-微生物组-大脑轴的潜力。此外,还讨论了解决先前研究中发现的问题的潜在策略。我们旨在为樟芝在脑神经病理学中的持续开发和利用提供概述。
    Prevalent neurological disorders such as Alzheimer\'s disease, Parkinson\'s disease, and stroke are increasingly becoming a global burden as society ages. It is well-known that degeneration and loss of neurons are the fundamental underlying processes, but there are still no effective therapies for these neurological diseases. In recent years, plenty of studies have focused on the pharmacology and feasibility of natural products as new strategies for the development of drugs that target neurological disorders. Antrodia camphorata has become one of the most promising candidates, and the crude extracts and some active metabolites of it have been reported to play various pharmacological activities to alleviate neurological symptoms at cellular and molecular levels. This review highlights the current evidence of Antrodia camphorata against neurological disorders, including safety evaluation, metabolism, blood-brain barrier penetration, neuroprotective activities, and the potential on regulating the gut-microbiome-brain axis. Furthermore, potential strategies to resolve problematic issues identified in previous studies are also discussed. We aim to provide an overview for the ongoing development and utilization of Antrodia camphorata in cerebral neuropathology.
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  • 文章类型: Journal Article
    植物旁乳杆菌P3(L.将具有良好抗真菌作用的无细胞上清液(CFS)喷洒在5°C和30°C储存的新鲜带壳花生上,以探讨其对新鲜带壳花生在储存过程中的微生物和品质的影响。结果表明,在降低真菌数量和霉变率的同时,旁草乳杆菌P3CFS有效地保持了鲜壳花生的良好品质,而且还改善了形态,颜色和味道。此外,植物旁乳杆菌P3CFS激活植物丝裂原活化蛋白激酶信号通路和植物激素信号通路,赤霉素调节蛋白等物质增强植物对病原微生物的抵抗力。植物旁乳杆菌P3CFS还可以诱导甘油磷脂和精氨酸的生物合成,从而增加新鲜花生的抗逆性。本研究为植物旁白乳杆菌P3CFS在鲜壳花生保鲜和防霉中的应用提供了研究数据。
    Lactiplantibacillus paraplantarum P3 (L. paraplantarum P3) cell-free supernatant (CFS) with good antifungal effect was sprayed on fresh in-shell peanuts stored at 5 °C and 30 °C to explore its effect on the microorganisms and quality of fresh in-shell peanuts during storage process. Results showed that L. paraplantarum P3 CFS effectively maintained good quality of fresh in-shell peanuts by not only reducing fungi amount and the mildew rate, but also improving the morphology, color and flavor. Besides, L. paraplantarum P3 CFS activated plant mitogen-activated protein kinase signaling pathway and plant hormone signaling pathway to produce more ethylene, gibberellin regulatory proteins and other substances to enhance plant resistance to pathogenic microorganisms. L. paraplantarum P3 CFS could also induce the biosynthesis of glycerophospholipid and arginine to increase the stress resistance of fresh peanuts. This study provides research data for the application of L. paraplantarum P3 CFS in the preservation and antimildew of fresh in-shell peanuts.
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  • 文章类型: Journal Article
    冬虫夏草是蚂蚁常见的致病真菌。一个新物种,O.Fusiformispora,基于来自五个基因的形态学和系统发育证据进行了描述(SSU,LSU,TEF1α,RPB1和RPB2)。梭形孢子的整个基因组,O.重叠群,O.Subtiliphialida,O.Satoi,O.flabellata,O.acrosasca,和O.camponoti-leonardi进行了测序和注释,并与O.landeralissensulato中其他物种的全基因组序列进行了比较。12个物种的基本全基因组特征表明,相关物种具有相似的GC含量和基因组大小。AntiSMASH和局部BLAST分析显示,推定的SMBGC的数量和类型,NPPS,PKS,12个物种的杂种PKS-NRPS结构域在同一属的不同物种之间存在显着差异。五个化合物的推定BGC,即,NG-391,lucilactaene,希格西宁B,吡啶甲酸A,并挖出了吡喃苷E。NG-391和lucilactaene是fusarinC的7-去甲基类似物。这12个基因组有共同的结构域,如KS-AT-DH-MT-ER-KR-ACP和SAT-KS-AT-PT-ACP-ACP-Te。SAT-KS-AT-PT-ACP-ACP-Te的ML和BI树与12种的多基因系统发育树高度一致。本研究提供了一种获得O.leneralissensulato物种及其在活文化基础上形成的无性的活文化的方法,这对于将来进一步研究O.landenalissensulato物种具有重要价值,同时也为进一步分析奥氏次生代谢产物奠定了基础。
    Ophiocordyceps unilateralis sensu lato is a common pathogenic fungus of ants. A new species, O. fusiformispora, was described based on morphology and phylogenetic evidence from five genes (SSU, LSU, TEF1α, RPB1, and RPB2). The whole genomes of O. fusiformispora, O. contiispora, O. subtiliphialida, O. satoi, O. flabellata, O. acroasca, and O. camponoti-leonardi were sequenced and annotated and compared with whole genome sequences of other species in O. unilateralis sensu lato. The basic genome-wide characteristics of the 12 species showed that the related species had similar GC content and genome size. AntiSMASH and local BLAST analyses revealed that the number and types of putative SM BGCs, NPPS, PKS, and hybrid PKS-NRPS domains for the 12 species differed significantly among different species in the same genus. The putative BGC of five compounds, namely, NG-391, lucilactaene, higginsianin B, pyripyropene A, and pyranonigrin E were excavated. NG-391 and lucilactaene were 7-desmethyl analogs of fusarin C. Furthermore, the 12 genomes had common domains, such as KS-AT-DH-MT-ER-KR-ACP and SAT-KS-AT-PT-ACP-ACP-Te. The ML and BI trees of SAT-KS-AT-PT-ACP-ACP-Te were highly consistent with the multigene phylogenetic tree in the 12 species. This study provided a method to obtain the living culture of O. unilateralis sensu lato species and its asexual formed on the basis of living culture, which was of great value for further study of O. unilateralis sensu lato species in the future, and also laid a foundation for further analysis of secondary metabolites of O. unilateralis sensu lato.
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