内生菌对植物次生代谢产物的转化

近年研究发现许多药用植物中的活性成分产量低下或副作用大、不利于人体吸收,而内生菌存在于健康植物的组织或器官中,可以对植物次生代谢产物进行转化且具有条件温和、专一有效、收效率高等特点。本文主要对近几年内生菌对植物次生代谢产物转化的研究进行综述和展望,以期为内生菌资源的开发和利用提供参考价值。     

肠道菌群代谢产物在鼠伤寒沙门菌感染中的作用研究进展

人和动物肠道内生存着多种多样的微生物群体,它们与宿主共同进化,对宿主的健康至关重要。肠道菌群可以发酵宿主难以消化的复杂碳水化合物,为宿主肠道细胞提供能量,同时其代谢产物对肠道病原菌沙门菌的感染产生着重要影响。正常情况下,肠道菌群代谢产物如丁酸与丙酸可以抑制沙门菌在肠道中的定植或者毒力基因的表达,而在肠道菌群受到扰乱时,其代谢的琥珀酸盐和1,2 丙二醇等物质却能促进沙门菌增殖。近年来,越来越多的研究揭示了肠道菌群代谢产物对沙门菌感染的影响。本综述通过总结近年来关于鼠伤寒沙门菌入侵时肠道菌群代谢产物改变的研究,综合阐述了肠道菌群代谢产物影响沙门菌感染的机制。     

中药调控肠道菌群代谢产物干预疾病研究进展

中药在预防和治疗疾病、改善机体健康方面发挥重要作用。中药化学组成复杂,调控途径和网络多样,极大阻碍了中药作用机理的阐明。人是由人体细胞与微生物组成的超级“共生体”。肠道菌群作为人体核心共生微生态系统,被称为人体的“第二基因组”和新的“器官”。肠道菌群稳态的变化在整体、系统层面上影响宿主健康和疾病进展。富含多糖、多酚等化学成分的中药可以调节肠道菌群代谢物,通过调控代谢产物及免疫信号介导的“肠-肝轴” “肠-脑轴”等通路防治疾病。本文综述了中药调控肠道菌群代谢产物与改善疾病的因果相关性和作用机制进展,为全面阐明中药治病防病作用机理和基于中药开发创新药物提供了指导和见解。     

素食对人类肠道菌群及其代谢产物作用的研究进展

为了探讨素食对肠道微环境的影响及其在维护机体健康中的作用,本文通过文献回顾分析了素食对肠道菌群多样性、潜在有益或有害菌属以及菌群代谢产物的影响。结果发现,素食能够调节肠道微环境,其中纯素、1–2周的短期素食以及某些疾病患者的素食影响更大。而对于肠道特定菌及代谢物,仅有益的普雷沃氏菌(Prevotella spp.)在素食者中显著高于杂食者,其余由于肠道菌群具有一定的个体差异均尚无定论,仍需进一步研究。     

溃疡性结肠炎肠道菌群及其代谢产物的研究进展

溃疡性结肠炎(UC)是一种病因尚未阐明的慢性非特异性肠道炎症疾病,多认为由易感人群免疫反应紊乱所致,疾病负担重,严重影响生活质量。近年随着人们生活方式的改变与诊断水平的提升,UC发病率和患病率逐年增加。研究显示肠道菌群及其代谢产物在UC的发生发展过程中起着关键作用,包括调节免疫、参与信号转导、保护肠黏膜屏障和营养代谢等,肠道菌群代谢产物的紊乱及微生态的失衡在炎症的形成及发展、免疫应激及稳态等方面产生重要影响。该文对近年来肠道菌群及其代谢产物与UC关系的相关研究作一综述,并探讨基于肠道菌群以及其代谢产物的UC防治策略。     

抗生素对肠道菌群及代谢影响的研究进展

抗生素的应用是作为治疗肠道和全身感染性疾病的支柱,而肠道菌群参与人体的多种生理功能。抗生素的使用可能会改变菌群的组成,影响菌群的代谢产物,如短链脂肪酸和脂多糖等,从而改变神经传导和肝脏生理功能。抗生素作用下肠道菌群的变化对血糖、血脂及机体免疫功能等产生影响,参与机体内环境的稳态。在脑−肠轴系统中,抗生素引起的菌群代谢产物的改变影响神经递质的表达,从而对宿主的神经精神状态产生影响。本文综述了抗生素作用下菌群组成的变化及其作用机制,以期为通过调控肠道菌群来治疗相关疾病提供新思路。

     

肠道菌群及其代谢产物与高血压的相关性研究进展

高血压是一种常见的慢性疾病, 是世界上最严重的公共卫生问题之一, 其发病机制尚未完全阐明。人体肠道菌群与疾病的发生相关, 高血压患者或高血压动物模型肠道中均存在菌群失调, 肠道菌群及其代谢产物被证明与高血压的发生密切相关。本文综述了国内外的相关研究进展, 从与高血压相关的肠道菌群种类、代谢产物及作用机制等多方面讨论了肠道菌群及其代谢产物与高血压的相关性, 以期从肠道菌群及其代谢产物的角度对高血压的防治提供思路和方法。

     

篮状菌属微生物次级代谢产物研究进展

天然产物的主要来源之一是微生物,不同于其他的生物资源,真菌菌种相对容易选育和保藏、适应力较强,可通过大规模发酵获取产物,更具有利于自然资源的可持续发展性和利用价值。篮状菌（Talaromyces sp.）及其次级代谢产物在天然色素上的研究受到科学家的青睐,同时在食品、环境、农业和医药等方面发挥了重要作用,尤其是海洋来源的篮状菌及其次级代谢物表现出显著的生物活性,例如杀虫、抗肿瘤、抗菌、抗病毒等。近来研究表明,篮状菌次级代谢产物根据生物合成的方式可以分为六大类：萜类（terpenes）、生物碱类（fumiquinazolines）、聚酮类（polyketides）、聚酯类（lactones）、醌类（quinones）和甾体类（steroids）,这些活性物质对促进药物的先导物质挖掘与开发具有重要意义。本文通过对文献和资料的查阅,总结了近年来篮状菌及其次级代谢物的研究开发进展,希望为后续研究和应用提供参考。     

植物内生菌活性代谢产物最新研究进展

内生菌广泛存在于植物组织中,作为一种新型的微生物资源,具有丰富的物种多样性,也是发掘新型天然活性物质的重要途径之一,有些内生菌还能产生与宿主植物相同或相似的活性成分。因此从植物内生菌中挖掘抗菌尤其抗临床耐药菌、抗肿瘤等天然活性产物不仅为新药的研发提供了新的方向,还能在一定程度上解决传统的天然产物药源——药用植物生长缓慢、资源紧缺等问题。从多个角度概述了近年来国内外报道的植物内生菌次生代谢产物及其来源、生物活性等方面的主要成果和最新进展,以期为植物内生菌活性代谢产物的研究提供参考。     

毛韧革菌次生代谢产物研究进展

毛韧革菌Stereum hirsutum是属于红菇目Russulales韧革菌科Stereaceae的一种木生担子菌,在我国分布广泛.过去70余年间从毛韧革菌中发现了112种次生代谢产物,主要包括倍半萜类、甾醇类、苯甲酸酯类、苯丙氨酸衍生物以及一些杂环化合物.这些化合物被证明具有抗氧化、抗肥胖、治疗糖尿病以及广泛的抗菌...     

Isoflavones with unusually modified B-rings and their evaluation as antiproliferative agents

Six novel isoflavone derivatives along with four known isoflavones were isolated from a culture of a highly nickel-resistant strain of Streptomyces mirabilis from a former uranium mining area. The structures of 7-hydroxy-3′,5′-dihydroxyisoflavone (5), 5,7-dihydroxy-3′,5′-dihydroxyisoflavone (6), 2′-hydroxy-3′-methoxygenistein (7), as well as hydroisoflavones A–C (8–10) were elucidated by MS and NMR analyses. Compounds 8–10 feature yet unprecedented types of non-aromatic, hydroxylated B rings, which result from plant isoflavone biotransformation. All new compounds display weak cytotoxic but potent antiproliferative activities. The anti-oestrogenic properties of 8 against MCF-7 human breast cancer cell line (GI₅₀: 6 μM) is even higher than the reference compound genistein.     

天然活性先导化合物生物转化研究进展

天然活性先导化合物生物转化是利用生物催化剂(如：酶、微生物、动植物细胞)将加入到生物反应系统中的天然活性先导化合物进行特异性的分子结构修饰以获得高效、低毒新化合物的方法。该方法可以有效地提高已知的天然活性先导化合物的活性、降低毒副作用、改善水溶性和生物利用度,也可以用来生产具有重要应用价值的微量天然活性先导化合物,同时可用于药物代谢机制的研究。国内外学者已经针对甾体、醌类、黄酮类、萜类等化合物开展了天然活性先导化合物生物转化研究,筛选出一批有重要应用价值的生物转化反应类型,但针对天然活性先导化合物生物转化的机制、生物转化过程工程以及生物转化产物活性等方面的研究较少。将现代生命科学技术(如：生物催化剂的定向改造、高通量筛选、组合生物转化、非水相生物转化)引入天然活性先导化合物生物转化研究中,必将推进天然活性先导化合物的快速发展。     

Chrysophaentins are competitive inhibitors of FtsZ and inhibit Z-ring formation in live bacteria

The bacterial cell division protein FtsZ polymerizes in a GTP-dependent manner to form a Z-ring that marks the plane of division. As a validated antimicrobial target, considerable efforts have been devoted to identify small molecule FtsZ inhibitors. We recently discovered the chrysophaentins, a novel suite of marine natural products that inhibit FtsZ activity in vitro. These natural products along with a synthetic hemi-chrysophaentin exhibit strong antimicrobial activity toward a broad spectrum of Gram-positive pathogens. To define their mechanisms of FtsZ inhibition and determine their in vivo effects in live bacteria, we used GTPase assays and fluorescence anisotropy to show that hemi-chrysophaentin competitively inhibits FtsZ activity. Furthermore, we developed a model system using a permeable Escherichia coli strain, envA1, together with an inducible FtsZ-yellow fluorescent protein construct to show by fluorescence microscopy that both chrysophaentin A and hemi-chrysophaentin disrupt Z-rings in live bacteria. We tested the E. coli system further by reproducing phenotypes observed for zantrins Z1 and Z3, and demonstrate that the alkaloid berberine, a reported FtsZ inhibitor, exhibits auto-fluorescence, making it incompatible with systems that employ GFP or YFP tagged FtsZ. These studies describe unique examples of nonnucleotide, competitive FtsZ inhibitors that disrupt FtsZ in vivo, together with a model system that should be useful for in vivo testing of FtsZ inhibitor leads that have been identified through in vitro screens but are unable to penetrate the Gram-negative outer membrane.     

Detoxification of polycyclic aromatic hydrocarbons by fungi

Summary The polycyclic aromatic hydrocarbons (PAHs) are a group of hazardous environmental pollutants, many of which are acutely toxic, mutagenic, or carcinogenic. A diverse group of fungi, includingAspergillus ochraceus, Cunninghamella elegans, Phanerochaete chrysosporium, Saccharomyces cerevisiae, andSyncephalastrum racemosum, have the ability to oxidize PAHs. The PAHs anthracene, benz[a]anthracene, benzo[a]pyrene, fluoranthene, fluorene, naphthalene, phenanthrene, and pyrene, as well as several methyl-, nitro-, and fluoro-substituted PAHs, are metabolized by one or more of these fungi. Unsubstituted PAHs are oxidized initially to arene oxides,trans-dihydrodiols, phenols, quinones, and tetralones. Phenols andtrans-dihydrodiols may be further metabolized, and thus detoxified, by conjugation with sulfate, glucuronic acid, glucose, or xylose. Although dihydrodiol epoxides and other mutagenic and carcinogenic compounds have been detected as minor fungal metabolites of a few PAHs, most transformations performed by fungi reduce the mutagenicity and thus detoxify the PAHs.     

Bioprocess Intensification for Production of Novel Marine Bacterial Antibiotics Through Bioreactor Operation and Design

There is a lack of research into bioreactor engineering and fermentation protocol design in the field of marine bacterial antibiotic production. Most production strategies are carried out at the shake-flask level and lack a mechanistic understanding of the antibiotic production process, offering poor prospects for successful scale-up. This review shows that data need to be collated on media and physical optima differences between the trophophase and idiophase, along with investigations into the control mechanisms for biosynthesis, to allow implementation of novel fermentation protocols. Immobilization may play a part in bioprocess intensification of marine bacterial antibiotic production, through again this area is understudied. Similarly, mass transfer and shear stress data of fermentations are needed to provide the bioreactor design requirements to intensify antibiotic biosynthesis, with process scale-up in mind. The application of bioprocess intensification methods to the production of antibiotics (and other metabolites) from marine microbes will become an important strategy for improving supply of natural products, in order to assess their suitability as chemotherapeutic drugs. Received March 11, 1999; accepted May 4, 1999.     

A one-pot enzymatic approach to the O-fluoroglucoside of N-methylanthranilate

In connection with prospective ¹⁸F-PET imaging studies, the potential for enzymatic synthesis of fluorine-labelled glycosides of small molecules was investigated. Approaches to the enzymatic synthesis of anomeric phosphates of d-gluco-configured fluorosugars proved ineffective. In contrast, starting in the d-galacto series and relying on the consecutive action of Escherichia coli galactokinase (GalK), galactose-1-phosphate uridylyltransferase (GalPUT), uridine-5′-diphosphogalactose 4-epimerase (GalE) and oat root glucosyltransferase (SAD10), a quick and effective synthesis of 6-deoxy-6-fluoro-d-glucosyl N-methylanthranilate ester was achieved.     

Analysis of chemical constituents from Polygonatum cyrtonema after “Nine-Steam-Nine-Bask” processing

Seven new compounds, known as polygonatine N₁‒N₇ (1‒7), and a known compound (8) were isolated from the ‘Nine-Steam-Nine-Bask’ processing product of Polygonatum cyrtonema Hua. The compounds’ structures were determined by spectroscopic analysis. All compounds were tested for dipeptidyl peptidase-4 (DPP-4) inhibition, glucose transport, and anti-inflammatory activities. Compound 8 suppressed NO production with an IC₅₀ of 35.4 μM.