Secondary Metabolism

次级代谢
  • 文章类型: Journal Article
    背景:天然产物是发现新生物农药以控制全球破坏性害虫AcyrthosiphonpisumHarris的重要来源。这里,通过全基因组测序和分析,从生物控制微生物Velezensis芽孢杆菌ZLP-101的次级代谢产物中发现并表征了杀虫物质。
    结果:基因组被注释,揭示了四个潜在的新基因簇和八个已知的次生代谢物合成基因簇的存在。粗提物,通过硫酸铵沉淀制备,通过暴露实验评估ZLP-101菌株对AcyrthosiphonpisumHarris蚜虫害虫的影响。菌株ZLP-101的粗提物对蚜虫的半致死浓度(LC50)为411.535mg/L。对杀虫机理的初步探索表明,粗提物通过胃毒对蚜虫的影响比通过接触对蚜虫的影响更大。Further,提取物影响酶活性,导致内部器官形成洞,同时变形,从而无法维持正常的生理活动,最终导致死亡。细胞外次生代谢产物的分离纯化结合质谱分析进一步鉴定粗提物的杀虫成分。共鉴定出15种杀虫活性化合物,包括iturins,fengycins,表面活性素,和spergualins。进一步的杀虫实验表明,表面活性素,iturin,和fengycin都表现出一定的杀螨活性,三者发挥协同致死作用。
    结论:这项研究提高了可用的葡萄芽孢杆菌基因组资源,并为全面研究葡萄芽孢杆菌ZLP-101的杀虫机理以及生物防治菌株中的活性成分奠定了基础。
    BACKGROUND: Natural products are important sources for the discovery of new biopesticides to control the worldwide destructive pests Acyrthosiphon pisum Harris. Here, insecticidal substances were discovered and characterized from the secondary metabolites of the bio-control microorganism Bacillus velezensis strain ZLP-101, as informed by whole-genome sequencing and analysis.
    RESULTS: The genome was annotated, revealing the presence of four potentially novel gene clusters and eight known secondary metabolite synthetic gene clusters. Crude extracts, prepared through ammonium sulfate precipitation, were used to evaluate the effects of strain ZLP-101 on Acyrthosiphon pisum Harris aphid pests via exposure experiments. The half lethal concentration (LC50) of the crude extract from strain ZLP-101 against aphids was 411.535 mg/L. Preliminary exploration of the insecticidal mechanism revealed that the crude extract affected aphids to a greater extent through gastric poisoning than through contact. Further, the extracts affected enzymatic activities, causing holes to form in internal organs along with deformation, such that normal physiological activities could not be maintained, eventually leading to death. Isolation and purification of extracellular secondary metabolites were conducted in combination with mass spectrometry analysis to further identify the insecticidal components of the crude extracts. A total of 15 insecticidal active compounds were identified including iturins, fengycins, surfactins, and spergualins. Further insecticidal experimentation revealed that surfactin, iturin, and fengycin all exhibited certain aphidicidal activities, and the three exerted synergistic lethal effects.
    CONCLUSIONS: This study improved the available genomic resources for B. velezensis and serves as a foundation for comprehensive studies of the insecticidal mechanism by Bacillus velezensis ZLP-101 in addition to the active components within biological control strains.
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  • 文章类型: Journal Article
    甜叶菊(甜叶菊)是菊科中的一种植物,含有几种生物活性化合物,包括抗糖尿病二萜苷(例如甜菊苷,莱鲍迪甙和杜克甙)可以作为零卡路里糖的替代品。在这项研究中,使用5%聚乙二醇(PEG)应用启发策略,氯化钠(NaCl;50和100mM)和赤霉酸(2.0和4.0mg/LGA3),以研究它们对芽形态发生的影响,和酚类物质的生产,黄酮类化合物,总可溶性糖,脯氨酸和甜菊糖,以及抗氧化活性,在S.rebaudiana的射击文化中。随此,添加2mg/L和4mg/LGA3的培养基表现出最高的射击反应(87%和80%)。较低浓度的GA3(2mg/L)与6-苄基氨基嘌呤(BAP)的组合增加导致最大平均芽长度(11.1cm)。向培养基中添加100mMNaCl盐导致观察到的最高总酚含量(TPC;4.11mg/g-DW,与对照0.52mg/g-DW相比)。培养的芽中总黄酮含量(TFC;1.26mg/g-DW)和多酚浓度(5.39mg/g-DW)。然而,在用50mMNaCl处理的培养基中生长的芽中观察到最大的抗氧化活性(81.8%)。与对照(0.37μg/mL)相比,施用2mg/L的GA3导致脯氨酸的最高积累(0.99μg/mL)。在补充有100mMNaCl和5%PEG的培养物中观察到最大甜菊糖苷含量(71µL/mL),然后是4mg/LGA3处理(70µL/mL),与对照(60µL/mL)相比。GA3与甜菊苷含量呈正相关。值得注意的是,这两种化合物来自共同的生化途径。这些结果表明,激发是增强甜菊糖苷和其他代谢物积累的有效选择,并为使用生物反应器的未来工业规模生产提供了基础。
    Stevia rebaudiana (stevia) is a plant in the Asteraceae that contains several biologically active compounds including the antidiabetic diterpene glycosides (e.g. stevioside, rebaudioside and dulcoside) that can serve as zero-calorie sugar alternatives. In this study, an elicitation strategy was applied using 5% polyethylene glycol (PEG), sodium chloride (NaCl; 50 and 100 mM) and gibberellic acid (2.0 and 4.0 mg/L GA3) to investigate their effect on shoot morphogenesis, and the production of phenolics, flavonoids, total soluble sugars, proline and stevioside, as well as antioxidant activity, in shoot cultures of S. rebaudiana. Herewith, the media supplemented with 2 mg/L and 4 mg/L GA3 exhibited the highest shooting response (87% and 80%). The augmentation of lower concentrations of GA3 (2 mg/L) in combination with 6-benzylaminopurine (BAP) resulted in the maximum mean shoot length (11.1 cm). The addition of 100 mM NaCl salts to the media led to the highest observed total phenolics content (TPC; 4.11 mg/g-DW compared to the control 0.52 mg/g-DW), total flavonoids content (TFC; 1.26 mg/g-DW) and polyphenolics concentration (5.39 mg/g-DW) in shoots cultured. However, the maximum antioxidant activity (81.8%) was observed in shoots raised in media treated with 50 mM NaCl. The application of 2 mg/L of GA3 resulted in the highest accumulation of proline (0.99 μg/mL) as compared to controls (0.37 μg/mL). Maximum stevioside content (71 µL/mL) was observed in cultures supplemented with 100 mM NaCl and 5% PEG, followed by the 4 mg/L GA3 treatment (70 µL/mL) as compared to control (60 µL/mL). Positive correlation was observed between GA3 and stevioside content. Notably, these two compounds are derived from a shared biochemical pathway. These results suggest that elicitation is an effective option to enhance the accumulation of steviosides and other metabolites and provides the groundwork for future industrial scale production using bioreactors.
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  • 文章类型: Journal Article
    深海环境,作为地球生物圈内相对未探索的极端,表现出与陆地栖息地的显著区别。为了在这些极端条件下茁壮成长,深海放线菌已经进化出独特的生化代谢和生理能力,以确保它们在这个生态位生存。在这项研究中,通过培养依赖性方法和16SrRNA测序方法,从马里亚纳海沟中分离并鉴定了5个放线菌菌株。微杆菌属的抗菌活性。B1075被发现是最有效的,因此,它被选为目标菌株。通过全球天然产品社会分子网络(GNPS)平台进行的分子网络分析确定了25种类黄酮化合物为类黄酮次生代谢产物。其中,金雀异黄素被纯化并鉴定为具有显著抗菌活性的生物活性化合物。基于全基因组测序数据,在菌株B1075中提出了金雀异黄素的完整合成途径,关键基因是CHS(编码查尔酮合成酶)。CHS基因的表达受到高静水压力的显著调控,从而影响菌株B1075中类黄酮化合物的产生,揭示了放线菌合成类黄酮次生代谢产物与其在分子水平上适应高压环境之间的关系。这些结果不仅扩大了我们对深海微生物的理解,而且有望为生物制药领域新型药物的开发提供有价值的见解。
    Deep-sea environments, as relatively unexplored extremes within the Earth\'s biosphere, exhibit notable distinctions from terrestrial habitats. To thrive in these extreme conditions, deep-sea actinomycetes have evolved unique biochemical metabolisms and physiological capabilities to ensure their survival in this niche. In this study, five actinomycetes strains were isolated and identified from the Mariana Trench via the culture-dependent method and 16S rRNA sequencing approach. The antimicrobial activity of Microbacterium sp. B1075 was found to be the most potent, and therefore, it was selected as the target strain. Molecular networking analysis via the Global Natural Products Social Molecular Networking (GNPS) platform identified 25 flavonoid compounds as flavonoid secondary metabolites. Among these, genistein was purified and identified as a bioactive compound with significant antibacterial activity. The complete synthesis pathway for genistein was proposed within strain B1075 based on whole-genome sequencing data, with the key gene being CHS (encoding chalcone synthase). The expression of the gene CHS was significantly regulated by high hydrostatic pressure, with a consequent impact on the production of flavonoid compounds in strain B1075, revealing the relationship between actinomycetes\' synthesis of flavonoid-like secondary metabolites and their adaptation to high-pressure environments at the molecular level. These results not only expand our understanding of deep-sea microorganisms but also hold promise for providing valuable insights into the development of novel pharmaceuticals in the field of biopharmaceuticals.
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  • 文章类型: Journal Article
    一种海洋真菌菌株,曲霉属。ITBBc1是从海南省南中国海收集的珊瑚中分离出来的。对该菌株的发酵提取物进行了深入的化学研究,提供了四种新的次级代谢产物(1-4),命名为甲磺酸甲-C和异戊烯基对苯苷H,连同四个已知的化合物(5-8)。通过广泛的光谱分析(包括一维和二维(1D和2D)NMR光谱和高分辨率电喷雾电离质谱(HR-ESI-MS))阐明了它们的结构。采用改进的Mosher方法来确定新化合物的绝对构型。植物毒性试验表明,化合物6-8对小麦和水稻种子萌发具有明显的拮抗活性,呈剂量依赖关系。
    A marine-derived fungal strain, Aspergillus sp. ITBBc1, was isolated from coral collected from the South China Sea in Hainan province. Intensive chemical investigation of the fermentation extract of this strain afforded four new secondary metabolites (1-4), named megastigmanones A-C and prenylterphenyllin H, along with four known compounds (5-8). Their structures were elucidated by extensive spectroscopic analysis including one-and two-dimensional (1D and 2D) NMR spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The modified Mosher\'s method was undertaken to determine the absolute configurations of new compounds. The phytotoxic activity test showed that compounds 6-8 exhibited significant antagonistic activity against the germination of Triticum aestivum L. and Oryza sativa L. seeds with a dose-dependent relationship.
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  • 文章类型: Journal Article
    六种新化合物,talamitonesA和B(1和2),去甲基他拉米酮B(3),talamiisocoumaringlycosidesA和B(4和5),和塔拉氨基萘糖苷(6),连同六个已知的化合物(7-12),从海洋真菌TalaromycesminnesotensisBTBU20220184中分离出。新结构通过HRESIMS和NMR表征。这是来自Talaromyces属真菌的异香精糖苷衍生物的首次报道。化合物5、6和9对金黄色葡萄球菌显示出协同抗菌活性。
    Six new compounds, talamitones A and B (1 and 2), demethyltalamitone B (3), talamiisocoumaringlycosides A and B (4 and 5), and talaminaphtholglycoside (6), together with six known compounds (7-12), were isolated from the marine-derived fungus Talaromyces minnesotensis BTBU20220184. The new structures were characterized by using HRESIMS and NMR. This is the first report of isocoumaringlycoside derivatives from a fungus of the Talaromyces genus. Compounds 5, 6, and 9 showed synergistic antibacterial activity against Staphylococcus aureus.
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  • 文章类型: Journal Article
    近年来,人们对研究与口服药物代谢相关的肠道微生物组来源的水解酶越来越感兴趣,特别是专注于天然产物药物。尽管天然产物药物在口服药物领域的重要性,缺乏关于肠道微生物组来源的水解酶与这些药物之间的调节相互作用的研究.本文从三个关键角度探讨了肠道微生物组来源的水解酶与天然产物药物代谢之间的相互作用。首先,它检查了糖苷水解酶的影响,酰胺水解酶,羧酸酯酶,胆汁盐水解酶,和环氧化物水解酶对天然产物结构的影响。其次,它探讨了天然产物药物如何影响微生物组衍生的水解酶。最后,它分析了水解酶和天然产物之间的相互作用对疾病发展的影响,以及开发微生物衍生酶的挑战。本综述的总体目标是为推进新型天然产物药物的研发和个性化治疗奠定坚实的理论基础。
    In recent years, there has been increasing interest in studying gut microbiome-derived hydrolases in relation to oral drug metabolism, particularly focusing on natural product drugs. Despite the significance of natural product drugs in the field of oral medications, there is a lack of research on the regulatory interplay between gut microbiome-derived hydrolases and these drugs. This review delves into the interaction between intestinal microbiome-derived hydrolases and natural product drugs metabolism from three key perspectives. Firstly, it examines the impact of glycoside hydrolases, amide hydrolases, carboxylesterase, bile salt hydrolases, and epoxide hydrolase on the structure of natural products. Secondly, it explores how natural product drugs influence microbiome-derived hydrolases. Lastly, it analyzes the impact of interactions between hydrolases and natural products on disease development and the challenges in developing microbial-derived enzymes. The overarching goal of this review is to lay a solid theoretical foundation for the advancement of research and development in new natural product drugs and personalized treatment.
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  • 文章类型: Journal Article
    虎尾草不仅是传统的中草药,也是来源多样的功能性食品。本研究旨在区分不同种类Balanophorae的生药学特征和次生代谢产物。收获了八种虎尾草,包括21批209个样品。采用超高效液相色谱-四极杆飞行时间质谱技术分析了21种来源的Balanophorae的次生代谢产物。进行靶向代谢组学分析以比较各组之间的差异。可以通过它们的生药学特征来鉴定rhopalocnemisphalloide和B。然后,在209个样品的混合提取物中鉴定或表征了41个次生代谢物,主要是酚酸,黄酮类化合物,以及它们的衍生物。这些次生代谢物的分布显示出不同物种之间的明显差异。此外,有针对性的代谢组学分析表明,七种Balanophorae的次级代谢谱显示出明显的差异,不同生长区域之间也存在差异。最后,筛选了5个重要的代谢标志物,以成功区分拉花芽孢杆菌,B.Harlandii,和B.多andra,包括三种酚酸和两种黄酮类化合物。这是第一个系统比较不同来源的Balanophorae的形态和次生代谢产物的研究,这可以为识别不同物种提供有效的信息。
    The Balanophorae are not only traditional Chinese herbal medicines but also functional foods with diverse sources. This study aimed to distinguish pharmacognostic characteristics and secondary metabolites among different species of Balanophorae. Eight species of Balanophorae herbs were harvested, including 21 batches with 209 samples. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used to analyze secondary metabolites of Balanophorae from 21 sources. Targeted metabolomic analysis was performed to compare differences among the groups. Rhopalocnemis phalloide and B. indica can be identified by their pharmacognostic characteristics. Then, 41 secondary metabolites were identified or characterized in the mixed extracts of the 209 samples, mainly phenolic acids, flavonoids, and their derivatives. The distribution of these secondary metabolites revealed apparent differences among different species. In addition, targeted metabolomic analysis suggested that the secondary metabolite profiles of seven species of Balanophorae showed noticeable differences, and differences were also observed among different growing regions. Finally, five important metabolic markers were screened to successfully distinguish B. laxiflora, B. harlandii, and B. polyandra, including three phenolic acids and two flavonoids. This is the first study to systematically compare both the morphology and secondary metabolites among different sources of Balanophorae, which could provide effective information for identifying diverse species.
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  • 文章类型: Journal Article
    内生真菌存在于每一种植物中,农作物也不例外。地球上有超过50,000种食用植物,但是只有15种作物提供了全球90%的能量摄入,和“四大”-小麦,大米,玉米和马铃薯是约50亿人的主食。这四种主要作物不仅有助于全球粮食安全,但是植物组织中的内生真菌是复杂的生态系统,一直受到审查。这篇综述概述了四种主要作物中的内生真菌及其次生代谢产物:小麦,大米,玉米和马铃薯.共从四大作物中鉴定出292株内生真菌,小麦的内生真菌数量最多,为157种。马铃薯内生真菌次生代谢产物数量最多,总共204种化合物,与其他三种含有内生真菌的作物仅23种次生代谢产物相比。一些化合物是具有特定结构和药理活性的化合物,这可能对农业化学和药物化学有益。
    Endophytic fungi are present in every plant, and crops are no exception. There are more than 50,000 edible plant species on the planet, but only 15 crops provide 90 percent of the global energy intake, and \"the big four\"-wheat, rice, maize and potato-are staples for about 5 billion people. Not only do the four staple crops contribute to global food security, but the endophytic fungi within their plant tissues are complex ecosystems that have been under scrutiny. This review presents an outline of the endophytic fungi and their secondary metabolites in four staple crops: wheat, rice, maize and potato. A total of 292 endophytic fungi were identified from the four major crops, with wheat having the highest number of 157 endophytic fungi. Potato endophytic fungi had the highest number of secondary metabolites, totaling 204 compounds, compared with only 23 secondary metabolites from the other three crops containing endophytic fungi. Some of the compounds are those with specific structural and pharmacological activities, which may be beneficial to agrochemistry and medicinal chemistry.
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  • 文章类型: Journal Article
    马兜铃属植物在学术和医学上都很重要。它属于木兰,系统发育位置不确定,并且是在被子植物全基因组WGD之后缺乏全基因组复制(WGD)事件的少数植物物种之一。A.contorta一直是一种重要的中药材料。由于它含有马兜铃酸(AAs),具有肾毒性和致癌性的化合物,这种植物的利用引起了广泛的关注。正在努力增加其生物活性化合物并减少或完全去除有毒化合物。MicroRNAs(miRNA)和天然反义转录物(NAT)是可能参与代谢调节的两类调节因子。这里,我们报告了223个miRNA和363个miRNA靶标的鉴定和表征。鉴定的miRNA包括属于20个家族的51个已知miRNA和属于107个家族的172个新miRNA。观察到miRNA的表达与其靶标之间呈负相关。此外,我们确定了441个A.contortaNAT和560个NAT感测转录本(ST)对,其中12个NAT是13个miRNA的靶标,形成18个miRNA-NAT-ST模块。各种miRNA和NAT可能通过miRNA-靶基因-酶基因的模式调节次级代谢,NAT-ST,和NAT-miRNA-靶基因-酶基因,表明A.contorta基因调控网络的复杂性。该结果为进一步控制其生物活性和毒性化合物的生产奠定了坚实的基础。
    Aristolochia contorta Bunge is an academically and medicinally important plant species. It belongs to the magnoliids, with an uncertain phylogenetic position, and is one of the few plant species lacking a whole-genome duplication (WGD) event after the angiosperm-wide WGD. A. contorta has been an important traditional Chinese medicine material. Since it contains aristolochic acids (AAs), chemical compounds with nephrotoxity and carcinogenicity, the utilization of this plant has attracted widespread attention. Great efforts are being made to increase its bioactive compounds and reduce or completely remove toxic compounds. MicroRNAs (miRNAs) and natural antisense transcripts (NATs) are two classes of regulators potentially involved in metabolism regulation. Here, we report the identification and characterization of 223 miRNAs and 363 miRNA targets. The identified miRNAs include 51 known miRNAs belonging to 20 families and 172 novel miRNAs belonging to 107 families. A negative correlation between the expression of miRNAs and their targets was observed. In addition, we identified 441 A. contorta NATs and 560 NAT-sense transcript (ST) pairs, of which 12 NATs were targets of 13 miRNAs, forming 18 miRNA-NAT-ST modules. Various miRNAs and NATs potentially regulated secondary metabolism through the modes of miRNA-target gene-enzyme genes, NAT-STs, and NAT-miRNA-target gene-enzyme genes, suggesting the complexity of gene regulatory networks in A. contorta. The results lay a solid foundation for further manipulating the production of its bioactive and toxic compounds.
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  • 文章类型: Journal Article
    盐碱胁迫限制植物生长并降低作物产量。土壤盐渍化和碱化严重威胁着农业的可持续发展和生态的良性循环。由植物生长促进根际细菌(PGPR)制成的生物肥料不仅可以增强植物的生长和胁迫耐受性,而且还具有环保和成本效益。已经有许多关于PGPRs增强植物耐盐性的潜在机制的研究。然而,关于碱钠胁迫下PGPR与植物之间的相互作用的知识有限。为了阐明PGPR提高植物对碱性钠胁迫的耐受性的潜在机制,我们从生长在碱性土壤中的当地植物的根际微生物中筛选出PGPR,并选择了高效菌株,以南方芽孢杆菌AD13-4为研究对象。我们的结果表明,菌株AD13-4可以产生各种促生长物质来调节植物内源激素水平,细胞分裂和分化,光合作用,抗氧化能力,等。转录组分析表明,菌株AD13-4显著影响代谢和次生代谢,信号转导,光合作用,氧化还原过程,和植物-病原体相互作用。在碱性钠条件下,菌株AD13-4的接种显着提高了植物生物量和代谢物的含量(例如,可溶性蛋白质和糖)以及次级代谢物(例如,酚类物质,黄酮类化合物,和萜类化合物)。16SrRNA基因测序结果表明,菌株AD13-4显著影响了根际微生物的丰度和组成,改善了土壤活性和理化性质。我们的研究为耐盐PGPR的优化提供了理论支持,也为阐明植物耐碱机理提供了有价值的信息。
    Saline and alkaline stresses limit plant growth and reduce crop yield. Soil salinization and alkalization seriously threaten the sustainable development of agriculture and the virtuous cycle of ecology. Biofertilizers made from plant growth-promoting rhizobacteria (PGPR) not only enhance plant growth and stress tolerance, but also are environmentally friendly and cost-effective. There have been many studies on the mechanisms underlying PGPRs enhancing plant salt resistance. However, there is limited knowledge about the interaction between PGPR and plants under alkaline-sodic stress. To clarify the mechanisms underlying PGPR\'s improvement of plants\' tolerance to alkaline-sodic stress, we screened PGPR from the rhizosphere microorganisms of local plants growing in alkaline-sodic land and selected an efficient strain, Bacillus altitudinis AD13-4, as the research object. Our results indicate that the strain AD13-4 can produce various growth-promoting substances to regulate plant endogenous hormone levels, cell division and differentiation, photosynthesis, antioxidant capacity, etc. Transcriptome analysis revealed that the strain AD13-4 significantly affected metabolism and secondary metabolism, signal transduction, photosynthesis, redox processes, and plant-pathogen interactions. Under alkaline-sodic conditions, inoculation of the strain AD13-4 significantly improved plant biomass and the contents of metabolites (e.g., soluble proteins and sugars) as well as secondary metabolites (e.g., phenols, flavonoids, and terpenoids). The 16S rRNA gene sequencing results indicated that the strain AD13-4 significantly affected the abundance and composition of the rhizospheric microbiota and improved soil activities and physiochemical properties. Our study provides theoretical support for the optimization of saline-alkali-tolerant PGPR and valuable information for elucidating the mechanism of plant alkaline-sodic tolerance.
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