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Microbiology (Reading, England) Nov 2019Antibiotic producing sense and respond to environmental signals by using nucleotide second messengers, including (p)ppGpp, cAMP, c-di-GMP and c-di-AMP. As summarized in... (Review)
Review
Antibiotic producing sense and respond to environmental signals by using nucleotide second messengers, including (p)ppGpp, cAMP, c-di-GMP and c-di-AMP. As summarized in this review, these molecules are important message carriers that coordinate the complex morphological transition from filamentous growth to sporulation along with the secondary metabolite production. Here, we provide an overview of the enzymes that make and break these second messengers and suggest candidates for (p)ppGpp and cAMP enzymes to be studied. We highlight the target molecules that bind these signalling molecules and elaborate individual functions that they control in the context of development. Finally, we discuss open questions in the field, which may guide future studies in this exciting research area.
Topics: Bacterial Proteins; Cyclic AMP; Dinucleoside Phosphates; Gene Expression Regulation, Bacterial; Guanine Nucleotides; Protein Binding; Second Messenger Systems; Spores, Bacterial; Streptomyces
PubMed: 31535967
DOI: 10.1099/mic.0.000846 -
Current Opinion in Microbiology Jun 2020Proteins that regulate transcription often also play an architectural role in the genome. Thus, it has been difficult to define with precision the distinctions between... (Review)
Review
Proteins that regulate transcription often also play an architectural role in the genome. Thus, it has been difficult to define with precision the distinctions between transcription factors and nucleoid-associated proteins (NAPs). Anachronistic descriptions of NAPs as 'histone-like' implied an organizational function in a bacterial chromatin-like complex. Definitions based on protein abundance, regulatory mechanisms, target gene number, or the features of their DNA-binding sites are insufficient as marks of distinction, and trying to distinguish transcription factors and NAPs based on their ranking within regulatory hierarchies or positions in gene-control networks is also unsatisfactory. The terms 'transcription factor' and 'NAP' are ad hoc operational definitions with each protein lying along a spectrum of structural and functional features extending from highly specific actors with few gene targets to those with a pervasive influence on the transcriptome. The Streptomyces BldC protein is used to illustrate these issues.
Topics: Bacterial Proteins; Binding Sites; Biological Evolution; DNA-Binding Proteins; Gene Expression Regulation, Bacterial; Genome, Bacterial; Protein Conformation; Streptomyces; Transcription Factors
PubMed: 32120333
DOI: 10.1016/j.mib.2020.01.019 -
Heredity Jul 2019Sixty years ago, the actinomycetes, which include members of the genus Streptomyces, with their bacterial cellular dimensions but a mycelial growth habit like fungi,... (Review)
Review
Sixty years ago, the actinomycetes, which include members of the genus Streptomyces, with their bacterial cellular dimensions but a mycelial growth habit like fungi, were generally regarded as a possible intermediate group, and virtually nothing was known about their genetics. We now know that they are bacteria, but with many original features. Their genome is linear with a unique mode of replication, not circular like those of nearly all other bacteria. They transfer their chromosome from donor to recipient by a conjugation mechanism, but this is radically different from the E. coli paradigm. They have twice as many genes as a typical rod-shaped bacterium like Escherichia coli or Bacillus subtilis, and the genome typically carries 20 or more gene clusters encoding the biosynthesis of antibiotics and other specialised metabolites, only a small proportion of which are expressed under typical laboratory screening conditions. This means that there is a vast number of potentially valuable compounds to be discovered when these 'sleeping' genes are activated. Streptomyces genetics has revolutionised natural product chemistry by facilitating the analysis of novel biosynthetic steps and has led to the ability to engineer novel biosynthetic pathways and hence 'unnatural natural products', with potential to generate lead compounds for use in the struggle to combat the rise of antimicrobial resistance.
Topics: Anti-Bacterial Agents; Biological Products; Chromosomes, Bacterial; DNA Replication; Genes, Bacterial; Genome, Bacterial; Polyketides; Recombination, Genetic; Streptomyces
PubMed: 31189905
DOI: 10.1038/s41437-019-0196-0 -
Molecules (Basel, Switzerland) Jan 2022The genus has been a rich source of bioactive natural products, medicinal chemicals, and novel drug leads for three-quarters of a century. Yet studies suggest that the... (Review)
Review
The genus has been a rich source of bioactive natural products, medicinal chemicals, and novel drug leads for three-quarters of a century. Yet studies suggest that the genus is capable of making some 150,000 more bioactive compounds than all secondary metabolites reported to date. Researchers around the world continue to explore this enormous potential using a range of strategies including modification of culture conditions, bioinformatics and genome mining, heterologous expression, and other approaches to cryptic biosynthetic gene cluster activation. Our survey of the recent literature, with a particular focus on the year 2020, brings together more than 70 novel secondary metabolites from species, which are discussed in this review. This diverse array includes cyclic and linear peptides, peptide derivatives, polyketides, terpenoids, polyaromatics, macrocycles, and furans, the isolation, chemical structures, and bioactivity of which are appraised. The discovery of these many different compounds demonstrates the continued potential of as a source of new and interesting natural products and contributes further important pieces to the mostly unfinished puzzle of Earth's myriad microbes and their multifaceted chemical output.
Topics: Macrolides; Multigene Family; Peptides; Polyketides; Secondary Metabolism; Streptomyces; Terpenes
PubMed: 35164153
DOI: 10.3390/molecules27030887 -
Natural Product Reports Feb 2023bacteria are a major microbial source of natural products, which are encoded within so-called biosynthetic gene clusters (BGCs). This highlight discusses the emergence... (Review)
Review
bacteria are a major microbial source of natural products, which are encoded within so-called biosynthetic gene clusters (BGCs). This highlight discusses the emergence of native s cell-free systems as a new tool to accelerate the study of the fundamental chemistry and biology of natural product biosynthesis from these bacteria. Cell-free systems provide a prototyping platform to study plug-and-play reactions in microscale reactions. So far, s cell-free systems have been used to rapidly characterise gene expression regulation, access secondary metabolite biosynthetic enzymes, and catalyse cell-free transcription, translation, and biosynthesis of example natural products. With further progress, we anticipate the development of more complex systems to complement existing experimental tools for the discovery and engineering of natural product biosynthesis from and related high G + C (%) bacteria.
Topics: Streptomyces; Cell-Free System; Biological Products; Multigene Family
PubMed: 36341536
DOI: 10.1039/d2np00057a -
FEMS Microbiology Reviews Nov 2020Chromosomes are dynamic entities, whose organization and structure depend on the concerted activity of DNA-binding proteins and DNA-processing enzymes. In bacteria,... (Review)
Review
Chromosomes are dynamic entities, whose organization and structure depend on the concerted activity of DNA-binding proteins and DNA-processing enzymes. In bacteria, chromosome replication, segregation, compaction and transcription are all occurring simultaneously, and to ensure that these processes are appropriately coordinated, all bacteria employ a mix of well-conserved and species-specific proteins. Unusually, Streptomyces bacteria have large, linear chromosomes and life cycle stages that include multigenomic filamentous hyphae and unigenomic spores. Moreover, their prolific secondary metabolism yields a wealth of bioactive natural products. These different life cycle stages are associated with profound changes in nucleoid structure and chromosome compaction, and require distinct repertoires of architectural-and regulatory-proteins. To date, chromosome organization is best understood during Streptomyces sporulation, when chromosome segregation and condensation are most evident, and these processes are coordinated with synchronous rounds of cell division. Advances are, however, now being made in understanding how chromosome organization is achieved in multigenomic hyphal compartments, in defining the functional and regulatory interplay between different architectural elements, and in appreciating the transcriptional control exerted by these 'structural' proteins.
Topics: Bacterial Proteins; Chromosomes, Bacterial; Streptomyces
PubMed: 32658291
DOI: 10.1093/femsre/fuaa028 -
Applied Microbiology and Biotechnology Jan 2021Streptomyces is one of the most versatile genera for biotechnological applications, widely employed as platform in the production of drugs. Although streptomycetes have... (Review)
Review
Streptomyces is one of the most versatile genera for biotechnological applications, widely employed as platform in the production of drugs. Although streptomycetes have a complex life cycle and metabolism that would need multidisciplinary approaches, review papers have generally reported only studies on single aspects like the isolation of new strains and metabolites, morphology investigations, and genetic or metabolic studies. Besides, even if streptomycetes are extensively used in industry, very few review papers have focused their attention on the technical aspects of biotechnological processes of drug production and bioconversion and on the key parameters that have to be set up. This mini-review extensively illustrates the most innovative developments and progresses in biotechnological production and bioconversion processes of antibiotics, immunosuppressant, anticancer, steroidal drugs, and anthelmintic agents by streptomycetes, focusing on the process development aspects, describing the different approaches and technologies used in order to improve the production yields. The influence of nutrients and oxygen on streptomycetes metabolism, new fed-batch fermentation strategies, innovative precursor supplementation approaches, and specific bioreactor design as well as biotechnological strategies coupled with metabolic engineering and genetic tools for strain improvement is described. The use of whole, free, and immobilized cells on unusual supports was also reported for bioconversion processes of drugs. The most outstanding thirty investigations published in the last 8 years are here reported while future trends and perspectives of biotechnological research in the field have been illustrated. KEY POINTS: • Updated Streptomyces biotechnological processes for drug production are reported. • Innovative approaches for Streptomyces-based biotransformation of drugs are reviewed. • News about fermentation and genome systems to enhance secondary metabolite production.
Topics: Actinomycetales; Biotechnology; Metabolic Engineering; Pharmaceutical Preparations; Streptomyces
PubMed: 33394149
DOI: 10.1007/s00253-020-11064-2 -
Microbiology (Reading, England) Oct 2019Gram-positive from the genus are best known for their morphological complexity and for their ability to produce numerous bioactive specialized metabolites with useful... (Review)
Review
Gram-positive from the genus are best known for their morphological complexity and for their ability to produce numerous bioactive specialized metabolites with useful applications in human and veterinary medicine and in agriculture. In contrast, the ability to infect living plant tissues and to cause diseases of root and tuber crops such as potato common scab (CS) is a rare attribute among members of this genus. Research on the virulence mechanisms of plant-pathogenic spp. has revealed the importance of the thaxtomin phytotoxins as key pathogenicity determinants produced by several species. In addition, other phytotoxic specialized metabolites may contribute to the development or severity of disease caused by spp., along with the production of phytohormones and secreted proteins. A thorough understanding of the molecular mechanisms of plant pathogenicity will enable the development of better management procedures for controlling CS and other plant diseases caused by the .
Topics: Bacterial Proteins; Bacterial Toxins; Plant Diseases; Plant Growth Regulators; Plant Tubers; Solanum tuberosum; Streptomyces; Virulence
PubMed: 31162023
DOI: 10.1099/mic.0.000818 -
World Journal of Microbiology &... Nov 2022Following the discovery of streptomycin from Streptomyces griseus in the 1940s by Selman Waksman and colleagues, aminoglycosides were first used to treat tuberculosis... (Review)
Review
Following the discovery of streptomycin from Streptomyces griseus in the 1940s by Selman Waksman and colleagues, aminoglycosides were first used to treat tuberculosis and then numerous derivatives have since been used to combat a wide variety of bacterial infections. These bactericidal antibiotics were used as first-line treatments for several decades but were largely replaced by ß-lactams and fluoroquinolones in the 1980s, although widespread emergence of antibiotic-resistance has led to renewed interest in aminoglycosides. The primary site of action for aminoglycosides is the 30 S ribosomal subunit where they disrupt protein translation, which contributes to widespread cellular damage through a number of secondary effects including rapid uptake of aminoglycosides via elevated proton-motive force (PMF), membrane damage and breakdown, oxidative stress, and hyperpolarisation of the membrane. Several factors associated with aminoglycoside entry have been shown to impact upon bacterial killing, and more recent work has revealed a complex relationship between metabolic states and the efficacy of different aminoglycosides. Hence, it is imperative to consider the environmental conditions and bacterial physiology and how this can impact upon aminoglycoside entry and potency. This mini-review seeks to discuss recent advances in this area and how this might affect the future use of aminoglycosides.
Topics: Aminoglycosides; Anti-Bacterial Agents; Drug Resistance, Microbial; Bacteria; Streptomyces griseus
PubMed: 36350431
DOI: 10.1007/s11274-022-03445-8 -
Current Opinion in Microbiology Jun 2022Division of labour occurs when different individuals, cells or tissues become specialised to perform complementary tasks that benefit the whole organism or social group.... (Review)
Review
Division of labour occurs when different individuals, cells or tissues become specialised to perform complementary tasks that benefit the whole organism or social group. Although long studied in multicellular organisms and colonies of social insects, several recent studies have established that division of labour is common in microorganisms. We review recent work on the division of labour in unicellular and multicellular bacteria, with a particular focus on reproductive and metabolic divisions of labour in actinomycetes. Actinomycetes show enormous variation in sporophore morphology and spore production patterns that likely affect the potential for cooperative interactions within colonies. They also display both irreversible genetic and spatiotemporally regulated phenotypic divisions of labour that structure antibiotic production. We highlight outstanding questions in this group of multicellular bacteria and outline factors that can modify the expression of division of labour across microbes.
Topics: Animals; Humans; Insecta; Reproduction; Streptomyces
PubMed: 35468363
DOI: 10.1016/j.mib.2022.102148