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Plants (Basel, Switzerland) Dec 2020strain CAI-21 has been previously reported to have plant growth-promotion abilities in chickpea, pigeonpea, rice, and sorghum. The strain CAI-21 and its secondary...
strain CAI-21 has been previously reported to have plant growth-promotion abilities in chickpea, pigeonpea, rice, and sorghum. The strain CAI-21 and its secondary metabolite were evaluated for their biocontrol potential against charcoal rot disease in sorghum caused by . Results exhibited that CAI-21 significantly inhibited the growth of the pathogen, , in dual-culture (15 mm; zone of inhibition), metabolite production (74% inhibition), and blotter paper (90% inhibition) assays. When CAI-21 was tested for its biocontrol potential under greenhouse and field conditions following inoculation of by toothpick method, it significantly reduced the number of internodes infected (75% and 45% less, respectively) and length of infection (75% and 51% less, respectively) over the positive control (only inoculated) plants. Under greenhouse conditions, scanning electron microscopic analysis showed that the phloem and xylem tissues of the CAI-21-treated shoot samples were intact compared to those of the diseased stem samples. The culture filtrate of the CAI-21 was purified by various chromatographic techniques, and the active compound was identified as "organophosphate" by NMR and MS. The efficacy of organophosphate was found to inhibit the growth of in the poisoned food technique. This study indicates that CAI-21 and its active metabolite organophosphate have the potential to control charcoal rot in sorghum.
PubMed: 33297539
DOI: 10.3390/plants9121727 -
Applied and Environmental Microbiology Aug 2020is well known for biosynthesis of secondary metabolites with diverse bioactivities. Although oils have been employed as carbon sources to produce polyketide antibiotics...
is well known for biosynthesis of secondary metabolites with diverse bioactivities. Although oils have been employed as carbon sources to produce polyketide antibiotics for several industrial strains, the intrinsic correlation between oil utilization and high production of antibiotics still remains unclear. In this study, we investigated the correlation between oil metabolism and salinomycin biosynthesis in ZD11, which employs soybean oil as the main carbon source. Comparative genomic analysis revealed the enrichment of genes related to triacylglycerol (TAG) metabolism in ZD11. Transcriptomic profiling further confirmed the enhancement of TAG metabolism and acyl coenzyme A biosynthesis in ZD11. Multiple secreted lipases, which catalyze TAG hydrolysis, were seen to be working in a synergistic and complementary manner in aiding the efficient and stable hydrolyzation of TAGs. Together, our results suggest that enhanced TAG hydrolysis and fatty acid degradation contribute to the high efficiency of oil utilization in ZD11 in order to provide abundant carbon precursors for cell growth and salinomycin biosynthesis. In order to obtain high-level production of antibiotics, oils have been used as the main carbon source for some strains. Based on multiomics analysis, this study provides insight into the relationship between triacylglycerol (TAG) metabolism and antibiotic biosynthesis in ZD11, an oil-preferring industrial strain. Our investigation into TAG hydrolysis yielded further evidence that this strain utilizes complicated strategies enabling an efficient TAG metabolism. In addition, a novel secreted lipase was identified that exhibited highly hydrolytic activity for medium- and long-chain TAGs. Our findings represent a good start toward clarifying the complicated relationship between TAG catabolism and high-level antibiotic production in the industrial strains.
Topics: Anti-Bacterial Agents; Coccidiostats; Oils; Pyrans; Streptomyces; Triglycerides
PubMed: 32532869
DOI: 10.1128/AEM.00763-20 -
Chemical Science Mar 2023Terpenoids comprise the most chemically and structurally diverse family of natural products. In contrast to the huge numbers of terpenoids discovered from plants and...
Terpenoids comprise the most chemically and structurally diverse family of natural products. In contrast to the huge numbers of terpenoids discovered from plants and fungi, only a relatively small number of terpenoids were reported from bacteria. Recent genomic data in bacteria suggest that a large number of biosynthetic gene clusters encoding terpenoids remain uncharacterized. In order to enable the functional characterization of terpene synthase and relevant tailoring enzymes, we selected and optimized an expression system based on a chassis. Through genome mining, 16 distinct bacterial terpene biosynthetic gene clusters were selected and 13 of them were successfully expressed in the chassis, leading to characterization of 11 terpene skeletons including three new ones, representing an ∼80% success rate. In addition, after functional expression of tailoring genes, 18 novel distinct terpenoids were isolated and characterized. This work demonstrates the advantages of a chassis which not only enabled the successful production of bacterial terpene synthases, but also enabled functional expression of tailoring genes, especially P450, for terpenoid modification.
PubMed: 37006697
DOI: 10.1039/d2sc06033g -
Microbiology Resource Announcements Jul 2022The genus is a promising source of biologically active secondary metabolites. Here, we report the complete genome sequence of Streptomyces albus strain G153. The...
The genus is a promising source of biologically active secondary metabolites. Here, we report the complete genome sequence of Streptomyces albus strain G153. The assembled genome comprised a single linear chromosome of 6.9 Mbp with a G+C content of 73.3%.
PubMed: 35652652
DOI: 10.1128/mra.00332-22 -
Journal of Biomedicine & Biotechnology 2012Cancer stem cells (CSCs) represent a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity and the ability to give rise to the... (Review)
Review
Cancer stem cells (CSCs) represent a subpopulation of tumor cells that possess self-renewal and tumor initiation capacity and the ability to give rise to the heterogenous lineages of malignant cells that comprise a tumor. CSCs possess multiple intrinsic mechanisms of resistance to chemotherapeutic drugs, novel tumor-targeted drugs, and radiation therapy, allowing them to survive standard cancer therapies and to initiate tumor recurrence and metastasis. Various molecular complexes and pathways that confer resistance and survival of CSCs, including expression of ATP-binding cassette (ABC) drug transporters, activation of the Wnt/β-catenin, Hedgehog, Notch and PI3K/Akt/mTOR signaling pathways, and acquisition of epithelial-mesenchymal transition (EMT), have been identified recently. Salinomycin, a polyether ionophore antibiotic isolated from Streptomyces albus, has been shown to kill CSCs in different types of human cancers, most likely by interfering with ABC drug transporters, the Wnt/β-catenin signaling pathway, and other CSC pathways. Promising results from preclinical trials in human xenograft mice and a few clinical pilote studies reveal that salinomycin is able to effectively eliminate CSCs and to induce partial clinical regression of heavily pretreated and therapy-resistant cancers. The ability of salinomycin to kill both CSCs and therapy-resistant cancer cells may define the compound as a novel and an effective anticancer drug.
Topics: Animals; Antineoplastic Agents; Clinical Trials as Topic; Humans; Neoplasms; Neoplastic Stem Cells; Pyrans; Translational Research, Biomedical
PubMed: 23251084
DOI: 10.1155/2012/950658 -
Angewandte Chemie (International Ed. in... Jun 2018Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due...
Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from S. scabies, along with genes encoding a promiscuous tryptophan synthase (TrpS) from Salmonella typhimurium, were assembled in a heterologous host Streptomyces albus. Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to "non-natural" product target compounds.
Topics: Biosynthetic Pathways; Gene Expression Regulation, Bacterial; Genes, Bacterial; Genetic Engineering; Indoles; Peptide Synthases; Piperazines; Plants; Salmonella typhimurium; Streptomyces; Tryptophan Synthase
PubMed: 29603527
DOI: 10.1002/anie.201801525 -
MicrobiologyOpen Jun 2020Actinomycetales, such as the genus Streptomyces, are well-known cell factories employed to produce a wide variety of secondary metabolites for industrial use. However,...
Actinomycetales, such as the genus Streptomyces, are well-known cell factories employed to produce a wide variety of secondary metabolites for industrial use. However, not only is the genetic engineering of Streptomyces more complicated and tedious than other model laboratory species, such as Escherichia coli, there is also a considerable lack of genetic tools, hindering its adoption as a common chassis for synthetic biology. In this work, 23 novel shuttle vectors are presented that follow the canonical SEVA (Standard European Vector Architecture) common architecture with the goal of increasing the genetic toolbox repertoire for Streptomyces and other actinomycetes. The ORI module of these plasmids is composed of the combination of two origins of replication, one for Gram-negative bacteria and the other for Streptomyces, a Gram-positive bacteria. Origins of replication have been included in the collection for integrative, low-copy number, and medium-to-high-copy number vectors for Streptomyces. Also, a new selection marker has been developed that confers resistance to apramycin. The functionality of these plasmids was tested via the heterologous expression of GFP and the heterologous production of the plant flavonoid apigenin in Streptomyces albus J1074, with successful results in both cases, therefore expanding the current repertoire of genetic manipulation tools in Streptomyces species.
Topics: Anti-Bacterial Agents; Apigenin; Bioreactors; Drug Resistance, Bacterial; Escherichia coli; Genetic Engineering; Genetic Vectors; Nebramycin; Plasmids; Replication Origin; Streptomyces
PubMed: 32170856
DOI: 10.1002/mbo3.1024 -
Antonie Van Leeuwenhoek Apr 2020Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an...
Cloning natural product biosynthetic gene clusters from cultured or uncultured sources and their subsequent expression by genetically tractable heterologous hosts is an essential strategy for the elucidation and characterisation of novel microbial natural products. The availability of suitable expression hosts is a critical aspect of this workflow. In this work, we mutagenised five endogenous biosynthetic gene clusters from Streptomyces albus S4, which reduced the complexity of chemical extracts generated from the strain and eliminated antifungal and antibacterial bioactivity. We showed that the resulting quintuple mutant can express foreign biosynthetic gene clusters by heterologously producing actinorhodin, cinnamycin and prunustatin. We envisage that our strain will be a useful addition to the growing suite of heterologous expression hosts available for exploring microbial secondary metabolism.
Topics: Anthraquinones; Bacteriocins; Biological Products; Cloning, Molecular; Gene Expression Regulation, Bacterial; Macrolides; Molecular Structure; Organic Chemicals; Peptides, Cyclic; Species Specificity; Streptomyces
PubMed: 31781915
DOI: 10.1007/s10482-019-01360-x -
Microbiology Resource Announcements Dec 2022Here, we report the complete genome sequence of Streptomyces albus strain INA 01303, which was isolated from the Salt Lake Tambukan (Russia). The genome consists of a...
Here, we report the complete genome sequence of Streptomyces albus strain INA 01303, which was isolated from the Salt Lake Tambukan (Russia). The genome consists of a linear 6,840,896-nucleotide chromosome. This strain is predicted to produce a range of novel secondary metabolites with antibiotic activity.
PubMed: 36383002
DOI: 10.1128/mra.00991-22 -
MSphere 2016species produce an incredible array of high-value specialty chemicals and medicinal therapeutics. A single species typically harbors ~30 biosynthetic pathways, but only...
species produce an incredible array of high-value specialty chemicals and medicinal therapeutics. A single species typically harbors ~30 biosynthetic pathways, but only a few them are expressed in the laboratory; thus, poor understanding of how natural-product biosynthesis is regulated is a major bottleneck in drug discovery. Antimycins are a large family of anticancer compounds widely produced by species, and their regulation is atypical compared to that of most other natural products. Here we demonstrate that antimycin production by S4 is regulated by FscRI, a PAS-LuxR family cluster-situated regulator of the polyene antifungal agent candicidin. We report that heterologous production of antimycins by is dependent on FscRI and show that FscRI activates the transcription of key biosynthetic genes. We also demonstrate through chromatin immunoprecipitation sequencing that FscRI regulation is direct, and we provide evidence that this regulation strategy is conserved and unique to short-form antimycin gene clusters. Our study provides direct evidence of the cross-regulation of disparate biosynthetic gene clusters specifying unrelated natural products and expands the paradigmatic understanding of the regulation of secondary metabolism. Natural products produced by members of the phylum underpin many industrially and medically important compounds; however, the majority of the ~30 biosynthetic pathways harbored by an average species are not expressed in the laboratory. Understanding the diversity of regulatory strategies controlling the expression of these pathways is therefore critical if their biosynthetic potential is to be explored for new drug leads. Our findings reveal that the candicidin cluster-situated regulator FscRI coordinately controls the biosynthesis of both candicidin and antimycin, which is the first observation of cross-regulation of disparate biosynthetic gene clusters specifying unrelated natural products. We anticipate that this will emerge as a major strategy by which members of the phylum coordinately produce natural products, which will advance our understanding of how the expression of secondary metabolism is controlled and will aid the pursuit of "silent" biosynthetic pathway activation.
PubMed: 27981234
DOI: 10.1128/mSphere.00305-16