茚满霉素类天然产物的研究进展

茚满霉素类天然产物是一类具有反式四氢茚满环(indan)结构的微生物次级代谢产物,该类化合物普遍具有良好的抗菌、杀虫以及抗肿瘤等生物活性,因而引起了药物化学家和生物学家的广泛兴趣。对1979年至今有关茚满霉素类化合物的天然发现、生物活性、化学合成以及生物合成等方面的研究进展进行综述,为该类抗生素的基础和应用研究提供科学参考。     

放线菌选育的最近动向

放线菌选育的动向可分为以下几方面:次级代谢系统抗菌素系微生物次级代谢产物。次级代谢产物的合成系统与基础代谢系统有关。链霉素及卡那霉素等氨基糖甙抗菌素均为糖衍生物;氯霉素等芳香环抗菌素是莽草酸的代谢产物;粘菌素及杆菌肽等抗菌素是多肽     

海洋微生物次级代谢产物生物合成的研究进展

海洋微生物次级代谢产物往往具有新颖的化学结构,蕴含着独特的生物合成途径、酶学机理和不同于陆生放线菌次级代谢产物的生物合成机制。自从2000年第一例海洋微生物天然产物enterocin的生物合成基因簇被阐明以来,迄今已克隆和鉴定了27种海洋微生物次级代谢产物的完整生物合成基因簇。这些次级代谢产物的生物合成主要源于四种途径,包括聚酮合酶途径,非核糖体肽合成酶途径,聚酮-非核糖体肽合成酶杂合途径,以及其他途径。本文综述了近年来一些重要海洋微生物活性次级代谢产物的生物合成途径,以及组合生物合成技术在海洋微生物次级代谢产物结构多样化方面的应用。     

海洋真菌次级代谢产物化学成分及生物活性的研究进展

目的介绍近年来对海洋真菌化学成分和生物活性的研究进展。方法检索国内外近几年关于海洋真菌次级代谢产物的文章,从其化学结构和生物活性方面对文献进行整理和综述。结果对海洋真菌次级代谢产物的结构类型及其活性予以综述。结论海洋微生物种类繁多,次级代谢产物丰富多样,是筛选新药的资源宝库,为海洋真菌的进一步研究和开发利用提供依据。     

含APD环缩酚酸肽类天然产物的研究进展

含有4-氨基-2,4-戊二烯酸的环缩酚酸肽类天然产物是一类包含酯键的环状多肽次级代谢产物,通常具有抗肿瘤、抗病原体等生物活性。此文根据国内外最新研究现状,介绍了这类物质的来源、结构、制备现状、生物活性以及开发前景。     

海绵共附生微生物活性次级代谢产物的研究进展

目的综述海绵共附生微生物次级代谢产物的生物活性及研究进展。方法查阅文献。进行整理和归纳。结果与结论从海绵共附生微生物中已分离得到许多结构独特，活性多样的次级代谢产物。其中有些具有潜在的药用价值。     

生物药物素及其寻找

微生物产生的次级代谢产物具有各种不同的生物活性,抗生素是人们熟悉的有抗微生物、抗肿瘤作用的微生物次级代谢产物。可是微生物产生的非抗生素的生物活性物质由于研究起步比较迟,所以人们对这类药物比较陌生。近年来,随着天然产物化学研究的广泛深入,随着越来越多疾病确定在分子学     

海洋来源的放线菌次级代谢产物及其生物活性

放线菌是迄今最重要和最大的药用微生物种群。海洋放线茵生存于苛刻特殊的海洋环境，使其具备了复杂独特的代谢途径，其次级代谢产物在结构类型以及在生物活性等方面都呈现出与陆生放线茵不同的特点和多样性。多年来，诸多结构新颖、生物活性显著的天然活性产物持续从海洋来源放线茵代谢产物中被发现，这些活性化合物为新药研究提供了丰富的先导化合物，有些已进入研发阶段。近年，海洋放线茵活性产物的研究仍然是海洋微生物产物研究中值得关注的一个热点。本文按化舍物结构类型简要介绍了海洋来源放线茵代谢产物及其生物活性的研究概况。     

海鞘微生物来源活性次级代谢产物研究进展

海鞘作为海洋药物的重要源泉,从中分离的8%的活性化合物被认为源自其共附生微生物。近年来,海鞘微生物来源次级代谢产物因其新颖的化学结构和显著活性而逐渐受到关注,在海洋药物研发中具有广阔的前景。本文综述了1994~2022年初报道的150个新的海鞘微生物天然产物的来源、化学结构及其生物活性,结构类型主要包括聚酮类、生物碱类、萜类和肽类等,并展望了海鞘微生物天然产物的发展方向。     

中国抗生素杂志第31卷1～12期（2006年）目次检索

进展、述评与专栏土壤环境基因组技术及其在新药发现中的应用闫珠君,崔晓龙,李铭刚,等31(1):1以酵母病毒杀伤系统为基础的抗病毒药物筛选模型叶燕锐,潘力31(8):449深海微生物的研究开发肖湘,王风平31(2):87微生物天然产物数据库的建立及应用姜威,司书毅,陈湘萍,等31(2):119小单孢菌及其产生的次级生物活性代谢产物程元荣,郑卫31(6):321海藻真菌次级代谢产物研究进展贾铁争,刘红兵,方玉春,等31(6):328微生物来源活性多糖的研究进展贺晓波,司书毅31(2):127抗真菌药物的研究进展刘正印,王爱霞31(2):69微生物次级代谢产物生物合成基因簇与药物创…     

Bacterial bioactive metabolites as therapeutic agents: From production to action

Bacterial metabolites are one of the primary sources of drugs that we currently use to treat several diseases. However, bacterial drug discovery and development is a challenging and time-consuming process, and the emergence of new diseases and the development of resistance to currently available drugs demand the discovery of new metabolites with better biological activities. The new advancements in microbial technology, omics, genome and metabolic engineering, synthetic biology and the interdisciplinary approach of these fields overcome the hurdles in drug discovery and heterologous synthesis from bacteria. The gut microbiome performs a vital role in sustaining human health and aids in tackling various diseases. The metabolites produced by the gut microbiome act as an energy source for colon epithelium, maintain pH, help in cell differentiation and induces apoptosis in abnormal cells. The review discusses about the bacterial derived bioactive compounds, advancements and technologies in bacterial synthesis of bioactive sources and genomic and synthetic biology methods for the bioprospecting of bacterial metabolites. Since the gut microbiome relates to colon health, we have also discussed the techniques comprising probiotics, prebiotics, microbiome transplantation, toxins, and bacteriocins capable of preventing and managing colon associated health condition. Future directions in bacterial bioactive metabolite production are also discussed.     

基于肠道微生物及其代谢产物的2型糖尿病治疗药物的研究进展

随着人类微生物组学研究的深入,肠道微生物在人类健康中的作用逐渐得到重视。作为人体内的隐形器官,肠道微生物参与机体的代谢调控,肠道微生物失调可能造成各种常见代谢紊乱疾病,如2型糖尿病等。通过微生物组学和代谢组学的联合分析,人们逐渐从机制上了解肠道微生物及其代谢衍生物与2型糖尿病的关系。与正常人群相比,2型糖尿病人群中肠道微生物的组成在变形菌门、拟杆菌门、厚壁菌门/拟杆菌门比值中发生了明显变化。肠道微生物产生的短链脂肪酸、氨基酸代谢衍生物可以作为信使调节机体的葡萄糖代谢,影响2型糖尿病的发生、发展。二甲双胍等2型糖尿病治疗药物通过与肠道微生物的相互作用来降低血糖。综述了肠道微生物及其代谢产物关联2型糖尿病治疗药物的研究进展。     

The human gut microbiome – a new and exciting avenue in cardiovascular drug discovery

ABSTRACT

Introduction: Over the past decade, numerous research efforts have identified the gut microbiota as a novel regulator of human metabolic syndrome and cardiovascular disease (CVD). With the elucidation of underlying molecular mechanisms of the gut microbiota and its metabolites, the drug-discovery process of CVD therapeutics might be expedited.

Areas covered: The authors describe the evidence concerning the impact of gut microbiota on metabolic disorders and CVD and summarize the current knowledge of the gut microbial mechanisms that underlie CVD with a focus on microbial metabolites. In addition, they discuss the potential impact of the gut microbiota on the drug efficacy of available cardiometabolic therapeutic agents. Most importantly, the authors review the role of the gut microbiome as a promising source of potential drug targets and novel therapeutics for the development of new treatment modalities for CVD. This review also presents the various effective strategies to investigate the gut microbiome for CVD drug-discovery approaches.

Expert opinion: With the elucidation of its causative role in cardiometabolic disease and atherosclerosis, the human gut microbiome holds promises as a reservoir of novel potential therapeutic targets as well as novel therapeutic agents, paving a new and exciting avenue in cardiovascular drug discovery.     

Mechanisms of gastrointestinal microflora on drug metabolism in clinical practice

Considered as an essential “metabolic organ”, intestinal microbiota plays a key role in human health and the predisposition to diseases. It is an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract. Since the 20th century, researches have showed that intestinal microbiome possesses a variety of metabolic activities that are able to modulate the fate of more than 30 approved drugs and immune checkpoint inhibitors. These drugs are transformed to bioactive, inactive, or toxic metabolites by microbial direct action or host-microbial co-metabolism. These metabolites are responsible for therapeutic effects exerted by these drugs or side effects induced by these drugs, even for death. In view of the significant effect on the drugs metabolism by the gut microbiota, it is pivotal for personalized medicine to explore additional drugs affected by gut microbiota and their involved strains for further making mechanism clear through suitable animal models. This review mainly focus on specific mechanisms involved, with reference to the current literature about drugs metabolism by related bacteria or its enzymes available.     

A novel therapeutic target, GPR43; Where it stands in drug discovery

With growing interest in human microbiome for its implication in metabolic disorders, inflammatory diseases, immune disorders and so forth, understanding the biology at the interface of the gut flora and the host becomes very important for identifying novel therapeutic avenues. GPR43 has been deorphanized and the metabolites of microbiome, such as short-chain fatty acids, serve as its natural ligands. There are numerous reports that GPR43 might be a crucial link to the novel therapies for the unmet medical needs and many drug discovery organizations are making their moves in response.     

Potential Implications of Gut Microbiota in Drug Pharmacokinetics and Bioavailability

Gut microbial communities are capable of enzymatically transforming pharmaceutical compounds into active, inactive, and toxic metabolites, thus potentially affecting the pharmacokinetics and bioavailability of orally administered medications. Our understanding of the impact and clinical relevance of how gut microbial communities can directly and indirectly affect drug metabolism and, ultimately, clinical outcomes, is limited. Interindividual variability of gut microbial composition may partially explain differences observed in drug efficacy and toxicity in certain patient populations. This review provides an overview of how gut microbial communities can potentially contribute to individual drug response. This review focuses on the current landscape of clinical and preclinical research that defines the microbiome contribution on medication response with the goal of improving medication efficacy and decreasing medication toxicity.     

肠道菌群与放疗敏感性及放射性黏膜炎关系的研究进展

肠道菌群在肿瘤治疗中的作用在近几年受到广泛关注，包括化疗及免疫治疗在内的抗肿瘤治疗疗效均受到肠道菌群的调节。放疗是抗肿瘤中的重要组成部分，其疗效及不良反应发生风险受到多种因素的影响。近期研究表明，肠道菌群通过调节机体免疫系统影响放疗敏感性以及放射性黏膜炎的严重程度。该文系统地回顾了描述肠道菌群调节放疗疗效及其黏膜毒性的研究，希望通过调节肠道菌群以提高放疗疗效并减轻放疗副反应。     

药物微生物组在新药研发中的应用

药物基因组学研究宿主基因层面对药物安全性与有效性的作用,指导新药研发过程。但宿主基因层面不能完全解释个体间药效差异。药物微生物组学是药物基因组学的重要扩展,研究肠道微生物对药物安全性与有效性的影响。目前与肠道微生物相关的大数据、多组学分析、粪菌移植、合成生物学等学科与技术已逐步在新药研发中应用,本文综述了新药研发的现状以及肠道微生物与药物相互作用,概括了目前肠道微生物相关药物的研发进展。     

肠道菌群失调与口腔疾病研究概述——以儿童龋齿为例

众所周知,微生物菌群失调与人体多种疾病密切相关。口腔和肠道作为人体两大微生物栖息地,在微生物相关疾病中发挥着重要作用。尽管口腔和肠道是通过胃肠道连接的连续区域,但由于口腔-肠道屏障的存在,口腔和肠道微生物分布得到很好的隔离。然而,在口腔-肠道屏障功能障碍的情况下,口腔微生物群可以转移到肠黏膜。相反,肠道菌群失调也会对口腔微生物组成造成一定影响。口腔到肠道和肠道到口腔的微生物易位可以重塑彼此的微生物生态系统,最终调节机体生理功能和病理过程。然而迄今为止,口腔-肠道微生物的相互作用在口腔疾病中的发病机制一直未被充分认识。本文中,我们将重点介绍口腔-肠道微生物串扰在口腔疾病及儿童龋齿中的作用,为后续通过操纵肠道微生物治疗口腔疾病和儿童龋齿提供理论依据。