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Streptomyces hygroscopicus

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
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...
June 6, 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
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
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
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
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
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...
December 1, 2016: Journal of Industrial Microbiology & Biotechnology
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
Hisayuki Komaki, Natsuko Ichikawa, Akio Oguchi, Moriyuki Hamada, Tomohiko Tamura, Nobuyuki Fujita, Ken-Ichiro Suzuki
The aim of this study is 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, their phenotypic data previously reported also support the synonymy...
October 28, 2016: International Journal of Systematic and Evolutionary Microbiology
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
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
Song Liu, Miao Wang, Guocheng Du, Jian Chen
BACKGROUND: Transglutaminases (TGase), which are synthesized as a zymogen (pro-TGase) in Streptomyces sp., are important enzymes in the food industry. Because this pro-peptide is essential for the correct folding of Streptomyces TGase, TGase is usually expressed in an inactive pro-TGase form, which is then converted to active TGase by the addition of activating proteases in vitro. In this study, Streptomyces hygroscopicus TGase was actively produced by Streptomyces lividans through promoter engineering and codon optimization...
October 28, 2016: BMC Biotechnology
Sandrine M A Lima, Janaína G S Melo, Gardênia C G Militão, Gláucia M S Lima, Maria do Carmo A Lima, Jaciana S Aguiar, Renata M Araújo, Raimundo Braz-Filho, Pascal Marchand, Janete M Araújo, Teresinha G Silva
Actinomycetes are known to produce numerous secondary bioactive metabolites of pharmaceutical interest. The purpose of this study was to isolate, characterize, and investigate the antibacterial, antifungal, and anticancer activities of metabolites produced by Actinobacteria isolated from the rhizosphere of Paullinia cupana. The Actinobacteria was identified as Streptomyces hygroscopicus ACTMS-9H. Based on a bioguided study, the methanolic biomass extract obtained from submerged cultivation had the most potent antibacterial, antifungal, and cytotoxic activities...
January 2017: Applied Microbiology and Biotechnology
Jinsong Feng, Jing Jiang, Yan Liu, Wei Li, Ramila Azat, Xiaodong Zheng, Wen-Wen Zhou
Validamycin A (Val-A) synthesized by Streptomyces hygroscopicus 5008 is widely used as a high-efficient antibiotic to protect plants from sheath blight disease. A novel fermentation strategy was introduced to stimulate Val-A production by adding oxygen carriers. About 58 % increase in Val-A production was achieved using liquid paraffin. Further, biomass, carbon source, metabolic genes, and metabolic enzymes were studied. It was also found that the supplementation of liquid paraffin increased the medium dissolved oxygen and intracellular oxidative stress level...
October 2016: Journal of Industrial Microbiology & Biotechnology
Wei Li, Jinsong Feng, Yan Liu, Jing Jiang, Xiaodong Zheng, Wen-Wen Zhou
Validamycin A (Val-A), produced by Streptomyces hygroscopicus 5008 in industrial fermentation, is one of the most widely used anti-fungal agro-antibiotics in Asia and high performance liquid chromatography (HPLC) assay is usually used to determine the production of Val-A. A new approach to determine Val-A by spectrophotometer is developed. During the fermentation of S. hygroscopicus 5008, a pigment secretion was found along with the Val-A biosynthesis. There was a stable relationship between the concentration of Val-A and spectral absorption (SA) value of this pigment at 450 nm, even in different fermentation cultures or conditions...
December 2016: Journal of Bioscience and Bioengineering
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