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Streptomyces hygroscopicus

Yu-Ru Zhao, Hong-Mei Li, Meilin Zhu, Jing Li, Tao Ma, Qiang Huo, Young-Soo Hong, Cheng-Zhu Wu
Heat shock protein 90 (Hsp90) is treated as a molecular therapeutic target for the prevention and treatment of cancer. Geldanamycin (GA) was the first identified natural Hsp90 inhibitor, but hepatotoxicity has limited its clinical application. Nevertheless, a new GA analog (WK-88-1) with the non-benzoquinone skeleton, obtained from the genetically engineered Streptomyces hygroscopicus , was found to haveanticancer activity against two human breast cancer cell lines.WK-88-1 produced concentration-dependent inhibition in cell proliferation, cell cycle arrest, and apoptosis inestrogen receptor (ER)-positive MCF-7 andER-negativeMDA-MB-231 cell lines...
April 6, 2018: Journal of Microbiology and Biotechnology
Antonio Rizzo, Dirk Trauner
An approach toward (-)-enterocin, an antibiotic isolated from Streptomyces hygroscopicus, is described. Its compact, heavily oxidized protoadamantane core represents a daunting challenge for an efficient synthesis. Convergent assembly of its 2-oxabicyclo[3.3.1]nonane core with a cuprate-mediated Barbier reaction is disclosed. Its functionalization to a suitable substrate for a biomimetic aldol to close the final ring of the natural product is evaluated.
March 19, 2018: Organic Letters
Fei Liu, Wei Li, Shangbo Hua, Ye Han, Zhihua Xu, Daiwei Wan, Yilin Wang, Weichang Chen, Yuting Kuang, Jianming Shi, Qiaoming Zhi
Nigericin, an antibiotic derived from Streptomyces hygroscopicus that works by acting as an H+, K+ and Pb2+ ionophore, has exhibited promising anticancer activity. The main purpose of this study is to investigate its inhibitory effects on Wnt/β-catenin signaling pathway in colorectal cancer (CRC) cells and clarify the underlying mechanism. We exposed two CRC lines (SW620 and KM12) to increasing concentrations of nigericin for different time periods and the 50% inhibiting concentration (IC50) values were evaluated...
February 26, 2018: Molecular Cancer Therapeutics
Alireza Bolourian, Zahra Mojtahedi
Resistance to a drug and the suppression of inflammatory disorders with immunosuppressive drugs might have happened upon exposure to natural compounds during evolution. Streptomycetes are soil bacteria, but they produce therapeutic drugs. They have been reported to be the low-abundant members of mucosal microbiomes with a higher prevalence in nonhumans ingesting soil compared to humans. Their lower abundance in the human microbiome might be the representations of our current hygienic lifestyle. We suggest that the Streptomyces bacteria producing antiproliferative/immunosuppressive compounds (e...
January 26, 2018: Environmental Microbiology Reports
Wenjie Wan, Donglan He, Zhijun Xue, Zewen Zhang
Microbial transglutaminase (MTG) gene (mtg) from Streptomyces hygroscopicus H197 strain was cloned by PCR and mutated by deleting a specific 84 bp fragment using overlapping extension PCR. The mutant MTG and the wild MTG genes expressed by recombinant plasmid pET32a+- mutant mtg and pET32a+ -mtg, respectively, and were harvested by alternating freeze-thaw steps and purified by Ni column. The purified mutant MTG and the wild MTG exhibited 0.22 U/mg and 0.16 U/mg activity, respectively, and 0.69 U/mg and 0.54 U/mg activity, respectively, after activated by trypsin...
December 2017: Journal of Biosciences
Raquel G Soengas, Gustavo da Silva, Juan Carlos Estévez
Spironucleosides are a type of conformationally restricted nucleoside analogs in which the anomeric carbon belongs simultaneously to the sugar moiety and to the base unit. This locks the nucleic base in a specific orientation around the N-glycosidic bond, imposing restrictions on the flexibility of the sugar moiety. Anomeric spiro-functionalized nucleosides have gained considerable importance with the discovery of hydantocidin, a natural spironucleoside isolated from fermentation broths of Streptomyces hygroscopicus which exhibits potent herbicidal activity...
November 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Shanwen Jiang, Chenyu Piao, Yang Yu, Peng Cao, Chenxu Li, Fan Yang, Mutong Li, Wensheng Xiang, Chongxi Liu
A novel actinomycete, designated strain 1H-SSA4(T), was isolated from the head of an ant (Camponotus japonicus Mayr) and was found to produce angucyclinone antibiotics. A polyphasic approach was used to determine the taxonomic status of strain 1H-SSA4(T). The DNA G+C content of the draft genome sequence, consisting of 11.4 Mbp, was 70.0 mol%. 16S rRNA gene sequence similarity studies showed that strain 1H-SSA4(T) belongs to the genus Streptomyces with the highest sequence similarity to Streptomyces hygroscopicus subsp...
November 7, 2017: International Journal of Systematic and Evolutionary Microbiology
Li Cui, Karin Yanagi, Ting Shi, Zhang-Min Liu, Lin-Quan Bai, Yan Feng
Valienone is a significant natural carbasugar member of the C7-cyclitol family as a valuable precursor for glycosidase inhibitor drugs. It is an intermediate of validamycin A biosynthesis pathway and exhibits minimal accumulation in the fermentation broth of the natural Streptomyces producer. A quantitative analytical method is crucial for the development of a breakthrough microbial process overcoming the consumption of the natural metabolic flux. The present study was designed to develop a pre-column derivatization high-performance liquid chromatography method for quantification of valienone and to help establish a straightforward fermentation process for valienone production by metabolically engineered Streptomyces hygroscopicus 5008...
October 2017: Chinese Journal of Natural Medicines
Jing Jiang, Ya-Fang Sun, Xi Tang, Chao-Nan He, Ye-Lin Shao, Ya-Jie Tang, Wen-Wen Zhou
Validamycin A (Val-A) is produced by Streptomyces as a secondary metabolite with wide agricultural applications of controlling rice sheath blight, false smut and damping-off diseases. The effect of alkaline pH shock on enhancing Val-A production and its mechanism were investigated. A higher yield of Val-A was achieved by NaOH shock once or several times together with faster protein synthesis and sugar consumption and alkaline pH shock can increase Val-A production by 27.43%. Transcription of genes related to amino acid metabolism, carbon metabolism and electron respiratory chain was significantly up-regulated, accompanied by the substantial increase of respiratory activity and glutamate concentration...
October 6, 2017: Bioresource Technology
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...
December 2017: Nature Chemical Biology
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
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
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
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 polyketide synthase (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
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
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
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
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
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
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
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