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Streptomyces hygroscopicus

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https://www.readbyqxmd.com/read/28991239/stendomycin-selectively-inhibits-tim23-dependent-mitochondrial-protein-import
#1
Ireos Filipuzzi, Janos Steffen, Mitchel Germain, Laetitia Goepfert, Michael A Conti, Christoph Potting, Raffaele Cerino, Martin Pfeifer, Philipp Krastel, Dominic Hoepfner, Julie Bastien, Carla M Koehler, Stephen B Helliwell
Tim17 and Tim23 are the main subunits of the TIM23 complex, one of the two major essential mitochondrial inner-membrane protein translocon machineries (TIMs). No chemical probes that specifically inhibit TIM23-dependent protein import were known to exist. Here we show that the natural product stendomycin, produced by Streptomyces hygroscopicus, is a potent and specific inhibitor of the TIM23 complex in yeast and mammalian cells. Furthermore, stendomycin-mediated blockage of the TIM23 complex does not alter normal processing of the major regulatory mitophagy kinase PINK1, but TIM23 is required to stabilize PINK1 on the outside of mitochondria to initiate mitophagy upon membrane depolarization...
October 9, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28974216/metabolic-network-model-guided-engineering-ethylmalonyl-coa-pathway-to-improve-ascomycin-production-in-streptomyces-hygroscopicus-var-ascomyceticus
#2
Junhua Wang, Cheng Wang, Kejing Song, Jianping Wen
BACKGROUND: Ascomycin is a 23-membered polyketide macrolide with high immunosuppressant and antifungal activity. As the lower production in bio-fermentation, global metabolic analysis is required to further explore its biosynthetic network and determine the key limiting steps for rationally engineering. To achieve this goal, an engineering approach guided by a metabolic network model was implemented to better understand ascomycin biosynthesis and improve its production. RESULTS: The metabolic conservation of Streptomyces species was first investigated by comparing the metabolic enzymes of Streptomyces coelicolor A3(2) with those of 31 Streptomyces strains, the results showed that more than 72% of the examined proteins had high sequence similarity with counterparts in every surveyed strain...
October 3, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28968205/effect-of-immobilisation-on-production-of-rapamycin-by-streptomyces-hygroscopicus
#3
R Sinha, P Srivastava
Numerous antibiotics as secondary metabolites have been isolated from microbes specifically Streptomyces sp. Rapamycin is one of these, which exhibits many roles as immunosuppressant, antifungal antibiotic, anti-tumour etc. Constant thrust has been put by many researchers to improve the production of rapamycin by Streptomyces hygroscopicus. Past research show that whole cell immobilisation is a useful strategy for antibiotic production with economical advantage. This study is another attempt in this direction which involves immobilisation of producer organism on various supports such as polyutherane foam, sintered beads, glass beads and foam peanuts...
July 31, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28873206/characterization-and-phylogenetic-affiliation-of-actinobacteria-from-tropical-soils-with-potential-uses-for-agro-industrial-processes
#4
J C M Dornelas, J E F Figueiredo, C S de Abreu, U G P Lana, C A Oliveira, I E Marriel
Secondary metabolites produced by Actinobacteria of tropical soils represent a largely understudied source of novel molecules with relevant application in medicine, pharmaceutical and food industries, agriculture, and environmental bioremediation. The present study aimed to characterize sixty-nine Actinobacteria isolated from compost and tropical soils using morphological, biochemical, and molecular methods. All the isolates showed high variation for morphological traits considering the color of pigments of the aerial and vegetative mycelium and spore chain morphology...
August 31, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28731630/improved-pks-gene-expression-with-strong-endogenous-promoter-resulted-in-geldanamycin-yield-increase
#5
Xinran Wang, Xinjuan Ning, Qinqin Zhao, Qianjin Kang, Linquan Bai
The type I polyketide geldanamycin is a potent anti-tumor reagent. Its biosynthesis includes three steps: the biosynthesis of precursors, such as 3-amino-5-hydroxybenzoic acid (AHBA), the PKS chain extension, and the post-PKS modifications. According to the genomic and transcriptomic analysis, the PKS chain extension was deduced to be the rate-limiting step for geldanamycin production in Streptomyces hygroscopicus XM201. in order to improve the expression of PKS genes, a strong endogenous promoter 5063p was obtained based on the transcriptomic analysis and XylE enzymatic assay...
July 21, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28585046/gene-overexpression-in-streptomyces-hygroscopicus-associated-with-dna-amplification
#6
Guangxiang Cao, Peipei Zhang, Yuanxin Gu, Xiuhua Pang
The genetics of the Streptomyces hygroscopicus strain 10-22 is of interest due to the ability of this strain to produce antifungal compounds. Strain T110 was obtained through insertional mutagenesis of strain 10-22 and was found to have undergone DNA amplification, as determined by both conventional and pulsed-field gel electrophoresis (PFGE). pIJ702, the vector used for insertional mutagenesis, was shown to have integrated into and co-amplified with the chromosomal DNA sequence of T110, as pIJ702 hybridized predominantly with two of the three amplified BamHI fragments...
August 2017: Current Microbiology
https://www.readbyqxmd.com/read/28466297/insights-into-the-metabolic-mechanism-of-rapamycin-overproduction-in-the-shikimate-resistant-streptomyces-hygroscopicus-strain-uv-ii-using-comparative-metabolomics
#7
COMPARATIVE STUDY
Huiyan Geng, Huanhuan Liu, Jiao Liu, Cheng Wang, Jianping Wen
Rapamycin is a polyketide with a 31-membered macrolide ring that possesses powerful immunosuppressant activity. In this study, we firstly obtained a mutant, shikimate-resistant Streptomyces hygroscopicus strain UV-II, which displayed about 3.20-fold higher rapamycin production (305.9 mg/L) than the wild-type S. hygroscopicus ATCC29253 (95.5 mg/L). Under optimal conditions, with the addition of 2 g/L shikimic acid, the strain's rapamycin production was further increased by approximately 34.9%, to 412.6 mg/L...
June 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28455615/enhancement-of-antibiotic-productions-by-engineered-nitrate-utilization-in-actinomycetes
#8
Sitong Meng, Hang Wu, Lei Wang, Buchang Zhang, Linquan Bai
Nitrate is necessary for primary and secondary metabolism of actinomycetes and stimulates the production of a few antibiotics, such as lincomycin and rifamycin. However, the mechanism of this nitrate-stimulating effect was not fully understood. Two putative ABC-type nitrate transporters were identified in Streptomyces lincolnensis NRRL2936 and verified to be involved in lincomycin biosynthesis. With nitrate supplementation, the transcription of nitrogen assimilation genes, nitrate-specific ABC1 transporter genes, and lincomycin exporter gene lmrA was found to be enhanced and positively regulated by the global regulator GlnR, whose expression was also improved...
July 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28400999/mtor-function-and-therapeutic-targeting-in-breast-cancer
#9
REVIEW
Stephen H Hare, Amanda J Harvey
The mTOR pathway was discovered in the late 1970s after the compound and natural inhibitor of mTOR, rapamycin was isolated from the bacterium Streptomyces hygroscopicus. mTOR is serine/threonine kinase belonging to the phosphoinositide 3-kinase related kinase (PIKK) family. It forms two distinct complexes; mTORC1 and mTORC2. mTORC1 has a key role in regulating protein synthesis and autophagy whilst mTORC2 is involved in regulating kinases of the AGC family. mTOR signaling is often over active in multiple cancer types including breast cancer...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28390015/approaches-towards-the-enhanced-production-of-rapamycin-by-streptomyces-hygroscopicus-mtcc-4003-through-mutagenesis-and-optimization-of-process-parameters-by-taguchi-orthogonal-array-methodology
#10
Subhasish Dutta, Bikram Basak, Biswanath Bhunia, Ankan Sinha, Apurba Dey
The present research was conducted to define the approaches for enhanced production of rapamycin (Rap) by Streptomyces hygroscopicus microbial type culture collection (MTCC) 4003. Both physical mutagenesis by ultraviolet ray (UV) and chemical mutagenesis by N-methyl-N-nitro-N-nitrosoguanidine (NTG) have been applied successfully for the improvement of Rap production. Enhancing Rap yield by novel sequential UV mutagenesis technique followed by fermentation gives a significant difference in getting economically scalable amount of this industrially important macrolide compound...
May 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28263400/comparative-studies-of-the-catalytic-mechanisms-of-two-chorismatases-ch-fkbo-and-ch-hyg5
#11
COMPARATIVE STUDY
Lihua Dong, Yongjun Liu
Chorismatase is an important enzyme involved in Shikimate pathway, which catalyzes the conversion of chorismate into pyruvate and (dihydro)-benzoic acid derivatives. According to the outcomes of catalytic reactions, chorismatases can be divided into three subfamilies: CH-Fkbo, CH-Hyg5 and CH-XanB2. Recently, the crystal structures of CH-Fkbo and CH-Hyg5 from Streptomyces hygroscopicus have been successfully obtained, allowing us to perform QM/MM calculations to explore the reaction details. Our calculation results support the proposal that CH-Fkbo and CH-Hyg5 employ different catalytic mechanisms and gave the mechanistic details...
June 2017: Proteins
https://www.readbyqxmd.com/read/28238083/elimination-of-indigenous-linear-plasmids-in-streptomyces-hygroscopicus-var-jinggangensis-and-streptomyces-sp-fr008-to-increase-validamycin-a-and-candicidin-productivities
#12
Chenyang Lu, Hang Wu, Xiurong Su, Linquan Bai
Giant linear plasmids, which replicate independently of the chromosomes, widely exist in actinobacteria. Previous studies mostly focused on the replication and evolution of the linear plasmids or the secondary metabolite gene clusters and the resistance gene clusters therein. However, the relationships of the linear plasmids to the productivities of secondary metabolites have not been studied. In this work, we developed a method to eliminate the indigenous linear plasmid pSHJG1 in Streptomyces hygroscopicus var...
February 25, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28110605/biosynthesis-of-nitrogen-containing-natural-products-c7n-aminocyclitols-and-bis-indoles-from-actinomycetes
#13
REVIEW
Shumpei Asamizu
Actinomycetes are a major source of bioactive natural products with important pharmaceutical properties. Understanding the natural enzymatic assembly of complex small molecules is important for rational metabolic pathway design to produce "artificial" natural products in bacterial cells. This review will highlight current research on the biosynthetic mechanisms of two classes of nitrogen-containing natural products, C7N aminocyclitols and bis-indoles. Validamycin A is a member of C7N aminocyclitol natural products from Streptomyces hygroscopicus...
May 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28095865/engineered-biosynthesis-of-milbemycins-in-the-avermectin-high-producing-strain-streptomyces-avermitilis
#14
Myoun-Su Kim, Wan-Je Cho, Myoung Chong Song, Seong-Whan Park, Kaeun Kim, Eunji Kim, Naryeong Lee, Sang-Jip Nam, Ki-Hoon Oh, Yeo Joon Yoon
BACKGROUND: Milbemycins, produced from Streptomyces hygroscopicus subsp. aureolacrimosus and Streptomyces bingchenggensis, are 16-membered macrolides that share structural similarity with avermectin produced from Streptomyces avermitilis. Milbemycins possess strong acaricidal, insecticidal, and anthelmintic activities but low toxicity. Due to the high commercial value of the milbemycins and increasing resistance to the avermectins and their derivatives, it is imperative to develop an efficient combinatorial biosynthesis system exploiting an overproduction host strain to produce the milbemycins and novel analogs in large quantities...
January 17, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/27966376/production-of-17-o-demethyl-geldanamycin-a-cytotoxic-ansamycin-polyketide-by-streptomyces-hygroscopicus-dem20745
#15
Aron Baksh, Bernhard Kepplinger, Hadiza A Isah, Michael R Probert, William Clegg, Corinne Wills, Michael Goodfellow, Jeff Errington, Nick Allenby, Michael J Hall
The actinomycete DEM20745, collected from non-rhizosphere soil adjacent to Paraserianthes falactaria trees (Cangkringan, Indonesia), is an efficient producer of the anticancer ansamycin polyketide 17-O-demethyl-geldanamycin (17-O-DMG), a biosynthetic precursor of the Hsp90 inhibitor geldanamycin (GDM). In DEM20745, 17-O-DMG is the major ansamycin product observed reaching a maximum titre of 17 mg/L in the fermentation broth. 17-O-DMG has the potential to be a key starting material for the semi-synthesis of GDM analogues for use in anticancer therapy...
December 14, 2016: Natural Product Research
https://www.readbyqxmd.com/read/27909940/enhancement-of-rapamycin-production-by-metabolic-engineering-in-streptomyces-hygroscopicus-based-on-genome-scale-metabolic-model
#16
Lanqing Dang, Jiao Liu, Cheng Wang, Huanhuan Liu, Jianping Wen
Rapamycin, as a macrocyclic polyketide with immunosuppressive, antifungal, and anti-tumor activity produced by Streptomyces hygroscopicus, is receiving considerable attention for its significant contribution in medical field. However, the production capacity of the wild strain is very low. Hereby, a computational guided engineering approach was proposed to improve the capability of rapamycin production. First, a genome-scale metabolic model of Streptomyces hygroscopicus ATCC 29253 was constructed based on its annotated genome and biochemical information...
February 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/27903647/the-production-and-utilization-of-gdp-glucose-in-the-biosynthesis-of-trehalose-6-phosphate-by-streptomyces-venezuelae
#17
Matías D Asención Diez, Farzana Miah, Clare E M Stevenson, David M Lawson, Alberto A Iglesias, Stephen Bornemann
Trehalose-6-phosphate synthase OtsA from streptomycetes is unusual in that it uses GDP-glucose as the donor substrate rather than the more commonly used UDP-glucose. We now confirm that OtsA from Streptomyces venezuelae has such a preference for GDP-glucose and can utilize ADP-glucose to some extent too. A crystal structure of the enzyme shows that it shares twin Rossmann-like domains with the UDP-glucose-specific OtsA from Escherichia coli However, it is structurally more similar to Streptomyces hygroscopicus VldE, a GDP-valienol-dependent pseudoglycosyltransferase enzyme...
January 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27902297/genome-analysis-based-reclassification-of-streptomyces-endus-and-streptomyces-sporocinereus-as-later-heterotypic-synonyms-of-streptomyces-hygroscopicus-subsp-hygroscopicus
#18
Hisayuki Komaki, Natsuko Ichikawa, Akio Oguchi, Moriyuki Hamada, Tomohiko Tamura, Nobuyuki Fujita, Ken-Ichiro Suzuki
The aim of this study was to reclarify the taxonomic relationship among Streptomyces hygroscopicus subsp. hygroscopicus, Streptomyces endus and Streptomyces sporocinereus. Whole genome shotgun sequencing was performed for the type strains of these three taxa. Average nucleotide identity and digital DNA-DNA hybridization values among the three taxa were greater than the thresholds for bacterial species delineation, indicating that they belong to the same genomospecies. In addition, the phenotypic data previously reported also support the synonymy...
February 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/27869289/integration-of-parallel-13-c-labeling-experiments-and-in-silico-pathway-analysis-for-enhanced-production-of-ascomycin
#19
Haishan Qi, Mengmeng Lv, Kejing Song, Jianping Wen
Herein, the hyper-producing strain for ascomycin was engineered based on (13) C-labeling experiments and elementary flux modes analysis (EFMA). First, the metabolism of non-model organism Streptomyces hygroscopicus var. ascomyceticus SA68 was investigated and an updated network model was reconstructed using (13) C- metabolic flux analysis. Based on the precise model, EFMA was further employed to predict genetic targets for higher ascomycin production. Chorismatase (FkbO) and pyruvate carboxylase (Pyc) were predicted as the promising overexpression and deletion targets, respectively...
May 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/27800124/draft-genome-sequence-of-streptomyces-sp-tp-a0867-an-alchivemycin-producer
#20
Hisayuki Komaki, Natsuko Ichikawa, Akio Oguchi, Moriyuki Hamada, Enjuro Harunari, Shinya Kodani, Nobuyuki Fujita, Yasuhiro Igarashi
Streptomyces sp. TP-A0867 (=NBRC 109436) produces structurally complex polyketides designated alchivemycins A and B. Here, we report the draft genome sequence of this strain together with features of the organism and assembly, annotation, and analysis of the genome sequence. The 9.9 Mb genome of Streptomyces sp. TP-A0867 encodes 8,385 putative ORFs, of which 7,232 were assigned with COG categories. We successfully identified a hybrid polyketide synthase (PKS)/ nonribosomal peptide synthetase (NRPS) gene cluster that could be responsible for alchivemycin biosynthesis, and propose the biosynthetic pathway...
2016: Standards in Genomic Sciences
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