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The Brazilian Journal of Infectious... 2012Streptomyces is a genus of Gram-positive bacteria that grows in various environments, and its shape resembles filamentous fungi. The morphological differentiation of... (Review)
Review
Streptomyces is a genus of Gram-positive bacteria that grows in various environments, and its shape resembles filamentous fungi. The morphological differentiation of Streptomyces involves the formation of a layer of hyphae that can differentiate into a chain of spores. The most interesting property of Streptomyces is the ability to produce bioactive secondary metabolites, such as antifungals, antivirals, antitumorals, anti-hypertensives, immunosuppressants, and especially antibiotics. The production of most antibiotics is species specific, and these secondary metabolites are important for Streptomyces species in order to compete with other microorganisms that come in contact, even within the same genre. Despite the success of the discovery of antibiotics, and advances in the techniques of their production, infectious diseases still remain the second leading cause of death worldwide, and bacterial infections cause approximately 17 million deaths annually, affecting mainly children and the elderly. Self-medication and overuse of antibiotics is another important factor that contributes to resistance, reducing the lifetime of the antibiotic, thus causing the constant need for research and development of new antibiotics.
Topics: Anti-Bacterial Agents; Humans; Streptomyces
PubMed: 22975171
DOI: 10.1016/j.bjid.2012.08.014 -
Current Opinion in Biotechnology Oct 2022Streptomyces is one of the most relevant genera in biotechnology, and its rich secondary metabolism is responsible for the biosynthesis of a plethora of bioactive... (Review)
Review
Streptomyces is one of the most relevant genera in biotechnology, and its rich secondary metabolism is responsible for the biosynthesis of a plethora of bioactive compounds, including several clinically relevant drugs. The use of Streptomyces species for the manufacture of natural products has been established for more than half a century; however, the tremendous advances observed in recent years in genetic engineering and molecular biology have revolutionised the optimisation of Streptomyces as cell factories and drastically expanded the biotechnological potential of these bacteria. Here, we illustrate the most exciting advances reported in the past few years, with a particular focus on the approaches significantly improving the biotechnological capacity of Streptomyces to produce clinical drugs and other valuable secondary metabolites.
Topics: Biotechnology; Genetic Engineering; Secondary Metabolism; Streptomyces
PubMed: 35908316
DOI: 10.1016/j.copbio.2022.102762 -
Microbial Biotechnology Mar 2011
Topics: Anti-Bacterial Agents; Bacterial Proteins; Gene Expression Regulation, Bacterial; Streptomyces
PubMed: 21342459
DOI: 10.1111/j.1751-7915.2011.00255.x -
Research in Microbiology 2012High densities of antagonistic Streptomyces are associated with plant disease suppression in many soils. Here we review use of inoculation and organic matter amendments... (Review)
Review
High densities of antagonistic Streptomyces are associated with plant disease suppression in many soils. Here we review use of inoculation and organic matter amendments for enriching antagonistic Streptomyces populations to reduce plant disease and note that effective and consistent disease suppression in response to management has been elusive. We argue that shifting the focus of research from short-term disease suppression to the population ecology and evolutionary biology of antagonistic Streptomyces in soil will enhance prospects for effective management. A framework is presented for considering the impacts of short- and long-term management on competitive and coevolutionary dynamics among Streptomyces populations in relation to disease suppression.
Topics: Antibiosis; Plant Diseases; Plants; Soil Microbiology; Streptomyces
PubMed: 22922402
DOI: 10.1016/j.resmic.2012.07.005 -
Microbial Biotechnology Apr 2022Exporter engineering is a promising strategy to construct high-yield Streptomyces for natural product pharmaceuticals in industrial biotechnology. However, available...
Exporter engineering is a promising strategy to construct high-yield Streptomyces for natural product pharmaceuticals in industrial biotechnology. However, available exporters are scarce, due to the limited knowledge of bacterial transporters. Here, we built a workflow for exporter mining and devised a tunable plug-and-play exporter (TuPPE) module to improve the production of macrolide biopesticides in Streptomyces. Combining genome analyses and experimental confirmations, we found three ATP-binding cassette transporters that contribute to milbemycin production in Streptomyces bingchenggensis. We then optimized the expression level of target exporters for milbemycin titer optimization by designing a TuPPE module with replaceable promoters and ribosome binding sites. Finally, broader applications of the TuPPE module were implemented in industrial S. bingchenggensis BC04, Streptomyces avermitilis NEAU12 and Streptomyces cyaneogriseus NMWT1, which led to optimal titer improvement of milbemycin A3/A4, avermectin B and nemadectin α by 24.2%, 53.0% and 41.0%, respectively. Our work provides useful exporters and a convenient TuPPE module for titer improvement of macrolide biopesticides in Streptomyces. More importantly, the feasible exporter mining workflow developed here might shed light on widespread applications of exporter engineering in Streptomyces to boost the production of other secondary metabolites.
Topics: Anti-Bacterial Agents; Biological Control Agents; Macrolides; Streptomyces
PubMed: 34437755
DOI: 10.1111/1751-7915.13883 -
International Journal of Environmental... Nov 2020The purpose of this study was to investigate streptomycete populations in desert and savanna ecozones in Sudan and to identify species based on 16S rRNA gene sequences....
The purpose of this study was to investigate streptomycete populations in desert and savanna ecozones in Sudan and to identify species based on 16S rRNA gene sequences. A total of 49 different phenotypes (22 from sites representing the desert and semi-desert ecozone; 27 representing the savanna ecozone) have been included in the study. The isolates were characterized phenotypically and confirmed using 16S rRNA gene sequence analysis. The two ecozones showed both similarities and uniqueness in the types of isolates. The shared species were in cluster 1 (, cluster 2 ( sp.), cluster 3 (-like), and cluster 7 (. The desert ecozone revealed unique species in cluster 9 ( sp.) and cluster 10 (). Whereas, the savanna ecozone revealed unique species in cluster 4 ( sp.), cluster 5 (), cluster 6 (), and cluster 8 ( sp.). Streptomycetes are widely distributed in both desert and the savanna ecozones and many of these require full descriptions. Extending knowledge on communities and their dynamics in different ecological zones and their potential antibiotic production is needed.
Topics: Cluster Analysis; Desert Climate; Genetic Variation; Grassland; Phylogeny; RNA, Ribosomal, 16S; Soil Microbiology; Streptomyces; Sudan
PubMed: 33255614
DOI: 10.3390/ijerph17238749 -
Applied and Environmental Microbiology Feb 2022New antimicrobial agents are urgently needed to combat the emergence and spread of multidrug-resistant bacteria. Activating the cryptic biosynthetic gene clusters for...
New antimicrobial agents are urgently needed to combat the emergence and spread of multidrug-resistant bacteria. Activating the cryptic biosynthetic gene clusters for actinomycete secondary metabolites can provide essential clues for research into new antimicrobial agents. An effective method for this purpose is based on drug resistance selection. This report describes interesting results for drug resistance selection using antibiotics that target DNA replication and can effectively potentiate secondary metabolite production by actinomycetes. Ofloxacin-resistant mutants were isolated from five different streptomycetes. Ofloxacin is an antibiotic that binds to DNA complexes and type II topoisomerase, causing double-stranded breaks in bacterial chromosomes. Physiological and genetic characterization of the mutants revealed that the development of ofloxacin resistance in streptomycetes leads to the emergence of various types of secondary metabolite-overproducing strains. In Streptomyces coelicolor A3(2), ofloxacin-resistant mutants that overproduced actinorhodin, undecylprodigiosin, or carotenoid were identified. An ofloxacin-resistant mutant that overproduces methylenomycin A, whose biosynthetic gene cluster is located on the endogenous plasmid, SCP1, also was isolated. These observations indicate that ofloxacin resistance activates biosynthetic genes on both chromosomes and endogenous plasmids. We also identified the mutations that are probably involved in the phenotype of ofloxacin resistance and secondary metabolite overproduction in S. coelicolor A3(2). Furthermore, we observed an interesting phenomenon in which several ofloxacin-resistant mutants overproduced antibiotics in the presence of ofloxacin. Based on these results, we present the unique physiological and genetic characteristics of ofloxacin-resistant mutants and discuss the importance and potential development of the new findings. The abuse or overuse of antibacterial agents for therapy and animal husbandry has caused an increased population of antimicrobial-resistant bacteria in the environment. Consequently, fewer effective antimicrobials are now available. Due to the depleted antibiotic pipeline, pandemic outbreaks caused by antimicrobial-resistant bacteria are deeply concerning, and the development of new antibiotics is now an urgent issue. Promising sources of antimicrobial agents include cryptic biosynthetic gene clusters for secondary metabolites in streptomycetes and rare actinomycetes. This study's significance is the development of an unprecedented activation method to accelerate drug discovery research on a global scale. The technique developed in this study could allow for simultaneous drug discovery in different countries, maximizing the world's microbial resources.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Multigene Family; Ofloxacin; Streptomyces; Streptomyces coelicolor
PubMed: 34936843
DOI: 10.1128/aem.02327-21 -
FEBS Open Bio Dec 2023Amino acid-based surfactants are valuable compounds for cosmetic formulations. The chemical synthesis of acyl amino acids is conventionally performed by the...
Amino acid-based surfactants are valuable compounds for cosmetic formulations. The chemical synthesis of acyl amino acids is conventionally performed by the Schotten-Baumann reaction using fatty acyl chlorides, but aminoacylases have also been investigated for use in biocatalytic synthesis with free fatty acids. Aminoacylases and their properties are diverse; they belong to different peptidase families and show differences in substrate specificity and biocatalytic potential. Bacterial aminoacylases capable of synthesis have been isolated from Burkholderia, Mycolicibacterium, and Streptomyces. Although several proteases and peptidases from S. griseus have been described, no aminoacylases from this species have been identified yet. In this study, we investigated two novel enzymes produced by S. griseus DSM 40236 . We identified and cloned the respective genes and recombinantly expressed an α-aminoacylase (EC3.5.1.14), designated SgAA, and an ε-lysine acylase (EC3.5.1.17), designated SgELA, in S. lividans TK23. The purified aminoacylase SgAA was biochemically characterized, focusing on its hydrolytic activity to determine temperature- and pH optima and stabilities. The aminoacylase could hydrolyze various acetyl amino acids at the N -position with a broad specificity regarding the sidechain. Substrates with longer acyl chains, like lauroyl amino acids, were hydrolyzed to a lesser extent. Purified aminoacylase SgELA specific for the hydrolysis of N -acetyl-l-lysine was unstable and lost its enzymatic activity upon storage for a longer period but could initially be characterized. The pH optimum of SgELA was pH 8.0. While synthesis of acyl amino acids was not observed with SgELA, SgAA catalyzed the synthesis of lauroyl-methionine.
Topics: Humans; Streptomyces lividans; Streptomyces griseus; Streptomyces; Amino Acids; Lysine
PubMed: 37879963
DOI: 10.1002/2211-5463.13723 -
Nature Communications Jan 2022Filamentous actinobacteria such as Streptomyces undergo two distinct modes of cell division, leading to partitioning of growing hyphae into multicellular compartments...
Filamentous actinobacteria such as Streptomyces undergo two distinct modes of cell division, leading to partitioning of growing hyphae into multicellular compartments via cross-walls, and to septation and release of unicellular spores. Specific determinants for cross-wall formation and the importance of hyphal compartmentalization for Streptomyces development are largely unknown. Here we show that SepX, an actinobacterial-specific protein, is crucial for both cell division modes in Streptomyces venezuelae. Importantly, we find that sepX-deficient mutants grow without cross-walls and that this substantially impairs the fitness of colonies and the coordinated progression through the developmental life cycle. Protein interaction studies and live-cell imaging suggest that SepX contributes to the stabilization of the divisome, a mechanism that also requires the dynamin-like protein DynB. Thus, our work identifies an important determinant for cell division in Streptomyces that is required for cellular development and sporulation.
Topics: Bacterial Proteins; Biological Phenomena; Cell Division; Cell Wall; Hyphae; Life Cycle Stages; Spores, Bacterial; Streptomyces
PubMed: 35013186
DOI: 10.1038/s41467-021-27638-1 -
Microbial Cell Factories Jul 2023Streptomyces are well known for their potential to produce various pharmaceutically active compounds, the commercial development of which is often limited by the low...
BACKGROUND
Streptomyces are well known for their potential to produce various pharmaceutically active compounds, the commercial development of which is often limited by the low productivity and purity of the desired compounds expressed by natural producers. Well-characterized promoters are crucial for driving the expression of target genes and improving the production of metabolites of interest.
RESULTS
A strong constitutive promoter, stnYp, was identified in Streptomyces flocculus CGMCC4.1223 and was characterized by its effective activation of silent biosynthetic genes and high efficiency of heterologous gene expression. The promoter stnYp showed the highest activity in model strains of four Streptomyces species compared with the three frequently used constitutive promoters ermEp*, kasOp*, and SP44. The promoter stnYp could efficiently activate the indigoidine biosynthetic gene cluster in S. albus J1074, which is thought to be silent under routine laboratory conditions. Moreover, stnYp was found suitable for heterologous gene expression in different Streptomyces hosts. Compared with the promoters ermEp*, kasOp*, and SP44, stnYp conferred the highest production level of diverse metabolites in various heterologous hosts, including the agricultural-bactericide aureonuclemycin and the antitumor compound YM-216391, with an approximately 1.4 - 11.6-fold enhancement of the yields. Furthermore, the purity of tylosin A was greatly improved by overexpressing rate-limiting genes through stnYp in the industrial strain. Further, the yield of tylosin A was significantly elevated to 10.30 ± 0.12 g/L, approximately 1.7-fold higher than that of the original strain.
CONCLUSIONS
The promoter stnYp is a reliable, well-defined promoter with strong activity and broad suitability. The findings of this study can expand promoter diversity, facilitate genetic manipulation, and promote metabolic engineering in multiple Streptomyces species.
Topics: Tylosin; Biological Products; Streptomyces; Promoter Regions, Genetic; Multigene Family
PubMed: 37443029
DOI: 10.1186/s12934-023-02136-9