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Impact of the first <Emphasis Type="Italic">Streptomyces</Emphasis> genome sequence on the discovery and production of bioactive substances 总被引:2,自引:0,他引:2
An important addition to the field of bacterial genomics is the recent publication of the complete genome sequence of Streptomyces coelicolor. This strain has been for some decades the model organism for streptomycetes and other filamentous actinomycetes, Gram-positive bacteria highly valuable for their ability to produce thousands of bioactive metabolites, many of which have found important applications in medicine and agriculture. We discuss here the impacts that the S. coelicolor genome sequence is likely to have on the production of bioactive metabolites by current industrial strains, on the possible development of future superhost(s) for the production of valuable drugs, and on the search for new bioactive substances from microbial sources. 相似文献
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链霉菌具有强大的次级代谢能力, 能够产生众多具有生物活性的次级代谢产物, 如目前广泛应用的抗生素、抗肿瘤药物以及免疫抑制剂等。在链霉菌中, 次级代谢产物的生物合成受到包括途径特异性、多效性以及全局性调控基因在内的多层次严格调控。关键调控基因的缺失或过表达可以显著影响次级代谢产物的生物合成, 提示对于链霉菌次级代谢重要调控基因的功能及其作用机制的研究具有巨大的潜在应用价值。其中, 作为细菌信号传导系统的双组分系统(Two-component system, TCS)一直是大家研究的关注点。越来越多的研究表明TCS在链霉菌次级代谢过程中发挥着全局性的调控功能。本文重点介绍链霉菌模式菌株——天蓝色链霉菌中TCS(包括典型TCS)、孤立的组氨酸蛋白激酶(HK)以及应答调控蛋白(RR)参与次级代谢调控的研究进展。这些TCS的功能鉴定及机制解析为工业链霉菌的定向遗传改造以提高重要次级代谢产物的含量提供了理论依据。 相似文献
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Production of secondary metabolites is a process influenced by several physico-chemical factors including nutrient supply, oxygenation, temperature and pH. These factors have been traditionally controlled and optimized in industrial fermentations in order to enhance metabolite production. In addition, traditional mutagenesis programs have been used by the pharmaceutical industry for strain and production yield improvement. In the last years, the development of recombinant DNA technology has provided new tools for approaching yields improvement by means of genetic manipulation of biosynthetic pathways. These efforts are usually focused in redirecting precursor metabolic fluxes, deregulation of biosynthetic pathways and overexpression of specific enzymes involved in metabolic bottlenecks. In addition, efforts have been made for the heterologous expression of biosynthetic gene clusters in other organisms, looking not only for an increase of production levels but also to speed the process by using rapidly growing and easy to manipulate organisms compared to the producing organism. In this review, we will focus on these genetic approaches as applied to bioactive secondary metabolites produced by actinomycetes. 相似文献
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放线菌与枯草芽孢杆菌的共培养及其对活性次生代谢产物的影响 总被引:2,自引:0,他引:2
为探讨共培养对放线菌产生活性次生代谢产物的影响,结合抗菌活性测定及HPLC-PDA分析,研究了22株放线菌的单培养及其与枯草芽孢杆菌的共培养发酵代谢产物的差异,并选取抗菌活性较强的链霉菌FXJ2.014进一步研究其代谢产物。发现FXJ2.014、FXJ1.296、AS4.1252三株菌与枯草芽孢杆菌共培养时产生其在相同条件下单培养时没有的物质,其中链霉菌FXJ2.014单培养时主要产生醌霉素A,共培养时产物中增加了醌霉素结构类似物FXJ2.014-HB。进一步的抗菌、抗肿瘤活性测定结果表明,两者的生物活性有较显著的差异,且FXJ2.014-HB对多种肿瘤细胞系的抑制活性普遍弱于高毒性的醌霉素A,为有潜力的细胞毒性较小的抗生素。共培养是一条很有希望的发掘放线菌活性次生代谢产物的新途径。 相似文献
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Streptomyces coelicolor is the genetically best characterized species of a populous genus belonging to the gram-positive Actinobacteria. Streptomycetes are filamentous soil organisms, well known for the production of a plethora of biologically active secondary metabolic compounds. The Streptomyces developmental life cycle is uniquely complex and involves coordinated multicellular development with both physiological and morphological differentiation of several cell types, culminating in the production of secondary metabolites and dispersal of mature spores. This review presents a current appreciation of the signaling mechanisms used to orchestrate the decision to undergo morphological differentiation, and the regulators and regulatory networks that direct the intriguing development of multigenomic hyphae first to form specialized aerial hyphae and then to convert them into chains of dormant spores. This current view of S.?coelicolor development is destined for rapid evolution as data from '-omics' studies shed light on gene regulatory networks, new genetic screens identify hitherto unknown players, and the resolution of our insights into the underlying cell biological processes steadily improve. 相似文献
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代谢组学(metabolomics)主要是研究生物体、组织、细胞的代谢物组分及检测其动态变化过程,是继基因组和蛋白组学后新兴的一门组学技术。代谢物是细胞调节过程中的最终产物,其水平被视为生物系统对遗传或环境变化的最终反映。通过合适的分析平台,准确定性、定量在复杂的生物中具有化学多样性的次生代谢物是代谢组学的一项重要工作。液相色谱-串联质谱技术(liquid chromatography-tandem mass spectrometry,LC-MS/MS)是代谢物质检测平台最常用的方法,也为植物次生代谢物的广泛应用研究提供了基础。本文主要从植物激素类、叶酸类、黄酮类等次生代谢物方面进行阐述,结合液质联用技术,简要论述不同次生代谢物检测技术的研究进展。 相似文献
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Bioactive compounds from marine actinomycetes 总被引:1,自引:0,他引:1
Actinomycetes are one of the most efficient groups of secondary metabolite producers and are very important from an industrial
point of view. Among its various genera, Streptomyces, Saccharopolyspora, Amycolatopsis, Micromonospora and Actinoplanes are the major producers of commercially important biomolecules. Several species have been isolated and screened from the
soil in the past decades. Consequently the chance of isolating a novel actinomycete strain from a terrestrial habitat, which
would produce new biologically active metabolites, has reduced. The most relevant reason for discovering novel secondary metabolites
is to circumvent the problem of resistant pathogens, which are no longer susceptible to the currently used drugs. Existence
of actinomycetes has been reported in the hitherto untapped marine ecosystem. Marine actinomycetes are efficient producers
of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, insecticidal
and enzyme inhibition. Bioactive compounds from marine actinomycetes possess distinct chemical structures that may form the
basis for synthesis of new drugs that could be used to combat resistant pathogens. 相似文献
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van Wezel GP Krabben P Traag BA Keijser BJ Kerste R Vijgenboom E Heijnen JJ Kraal B 《Applied and environmental microbiology》2006,72(8):5283-5288
Filamentous actinomycetes are commercially widely used as producers of natural products (in particular antibiotics) and of industrial enzymes. However, the mycelial lifestyle of actinomycetes, resulting in highly viscous broths and unfavorable pellet formation, has been a major bottleneck in their commercialization. Here we describe the successful morphological engineering of industrially important streptomycetes through controlled expression of the morphogene ssgA. This led to improved growth of many industrial and reference streptomycetes, with fragmentation of the mycelial clumps resulting in significantly enhanced growth rates in batch fermentations of Streptomyces coelicolor and Streptomyces lividans. Product formation was also stimulated, with a twofold increase in yield of enzyme production by S. lividans. We anticipate that the use of the presented methodology will make actinomycetes significantly more attractive as industrial and sustainable production hosts. 相似文献
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Ana M Calvo Richard A Wilson Jin Woo Bok Nancy P Keller 《Microbiology and molecular biology reviews》2002,66(3):447-59, table of contents
Filamentous fungi are unique organisms-rivaled only by actinomycetes and plants-in producing a wide range of natural products called secondary metabolites. These compounds are very diverse in structure and perform functions that are not always known. However, most secondary metabolites are produced after the fungus has completed its initial growth phase and is beginning a stage of development represented by the formation of spores. In this review, we describe secondary metabolites produced by fungi that act as sporogenic factors to influence fungal development, are required for spore viability, or are produced at a time in the life cycle that coincides with development. We describe environmental and genetic factors that can influence the production of secondary metabolites. In the case of the filamentous fungus Aspergillus nidulans, we review the only described work that genetically links the sporulation of this fungus to the production of the mycotoxin sterigmatocystin through a shared G-protein signaling pathway. 相似文献
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Katzer W Blackburn M Charman K Martin S Penn J Wrigley S 《Biochemical Engineering Journal》2001,7(2):127-134
The choice of small-scale fermentation systems contributes significantly to a successful scale-up. Creasing of flasks and the chosen shaker parameters influence the production of secondary metabolites in a strain- and even compound-specific manner. Using actinomycetes and fungi as model organisms the influence of the small-scale fermentation system on the production of various secondary metabolites is described and the effects on screening success and scale-up are considered. 相似文献
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Baltz RH 《Journal of industrial microbiology & biotechnology》2011,38(6):657-666
With the recent advances in DNA sequencing technologies, it is now feasible to sequence multiple actinomycete genomes rapidly
and inexpensively. An important observation that emerged from early Streptomyces genome sequencing projects was that each strain contains genes that encode 20 or more potential secondary metabolites, only
a fraction of which are expressed during fermentation. More recently, this observation has been extended to many other actinomycetes
with large genomes. The discovery of a wealth of orphan or cryptic secondary metabolite biosynthetic gene clusters has suggested
that sequencing large numbers of actinomycete genomes may provide the starting materials for a productive new approach to
discover novel secondary metabolites. The key issue for this approach to be successful is to find ways to turn on or turn
up the expression of cryptic or poorly expressed pathways to provide material for structure elucidation and biological testing.
In this review, I discuss several genetic approaches that are potentially applicable to many actinomycetes for this application. 相似文献
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粘细菌基因组学研究进展 总被引:3,自引:2,他引:1
粘细菌(Myxobacteria)隶属于δ变形菌纲(Deltaproteobacteria)的粘球菌目(Myxococcales),是一类革兰氏阴性杆状细菌。它是继放线菌和真菌之后又一重要的活性次级代谢产物产生菌,尽管如此,由于分离纯化困难,粘细菌的研究进展一直较为缓慢。随着测序技术的进步和生物信息学的应用,大量粘细菌基因组被完成测序和报道。本文对粘细菌研究意义及该类资源开发价值、分离培养存在的困难进行了阐述,对粘细菌基因组注释及目前已测菌株的全基因组进行了归纳总结,同时介绍了基因组学在粘细菌生态、捕食机制、子实体形成以及次级代谢产物合成方面的研究进展。本文有助于了解基因组学在粘细菌研究中的重要价值,为联合应用多组学技术深入研究粘细菌代谢机制和社会性行为提供了参考,对粘细菌基础研究、资源发掘和开发利用具有重要意义。 相似文献
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Ana M. Calvo Richard A. Wilson Jin Woo Bok Nancy P. Keller 《Microbiological reviews》2002,66(3):447-459
Filamentous fungi are unique organisms—rivaled only by actinomycetes and plants—in producing a wide range of natural products called secondary metabolites. These compounds are very diverse in structure and perform functions that are not always known. However, most secondary metabolites are produced after the fungus has completed its initial growth phase and is beginning a stage of development represented by the formation of spores. In this review, we describe secondary metabolites produced by fungi that act as sporogenic factors to influence fungal development, are required for spore viability, or are produced at a time in the life cycle that coincides with development. We describe environmental and genetic factors that can influence the production of secondary metabolites. In the case of the filamentous fungus Aspergillus nidulans, we review the only described work that genetically links the sporulation of this fungus to the production of the mycotoxin sterigmatocystin through a shared G-protein signaling pathway. 相似文献
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Unlocking Streptomyces spp. for Use as Sustainable Industrial Production Platforms by Morphological Engineering
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Gilles P. van Wezel Preben Krabben Bjrn A. Traag Bart J. F. Keijser Rob Kerste Erik Vijgenboom Josef J. Heijnen Barend Kraal 《Applied microbiology》2006,72(8):5283-5288
Filamentous actinomycetes are commercially widely used as producers of natural products (in particular antibiotics) and of industrial enzymes. However, the mycelial lifestyle of actinomycetes, resulting in highly viscous broths and unfavorable pellet formation, has been a major bottleneck in their commercialization. Here we describe the successful morphological engineering of industrially important streptomycetes through controlled expression of the morphogene ssgA. This led to improved growth of many industrial and reference streptomycetes, with fragmentation of the mycelial clumps resulting in significantly enhanced growth rates in batch fermentations of Streptomyces coelicolor and Streptomyces lividans. Product formation was also stimulated, with a twofold increase in yield of enzyme production by S. lividans. We anticipate that the use of the presented methodology will make actinomycetes significantly more attractive as industrial and sustainable production hosts. 相似文献
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Sweet home actinomycetes: The 1999 MDS Panlabs Lecture 总被引:1,自引:0,他引:1
R H Baltz 《Journal of industrial microbiology & biotechnology》2000,24(2):79-88
For the past 25 years, I have devoted most of my research efforts to the application of molecular genetics to yield improvement
and production of novel secondary metabolites in actinomycetes. My group at Lilly Research Laboratories worked with a variety
of Streptomyces species and with strains of Amycolatopsis and Saccharopolyspora. We developed molecular genetic tools to manipulate actinomycete genes, and applied them to important secondary metabolites,
including tylosin, daptomycin, vancomycin, chloroeremomycin, and spinosyns. In the early years, I helped establish recombinant
DNA technology to manufacture mammalian proteins, and more recently, helped implement microbial genomics as a research tool
for antibiotic discovery. In this paper, I review some highlights, primarily from the actinomycete work. Journal of Industrial Microbiology & Biotechnology (2000) 24, 79–88.
Received 25 October 1999/ Accepted in revised form 12 November 1999 相似文献