Shijiazhuang Pharmaceutical Group Co.

Shijiazhuang, China

Shijiazhuang Pharmaceutical Group Co.

Shijiazhuang, China
SEARCH FILTERS
Time filter
Source Type

Cao Y.-X.,Tianjin University | Qiao B.,Tianjin University | Lu H.,Hebei Zhongrun Pharmaceutical Co. | Lu H.,Shijiazhuang Pharmaceutical Group Co. | And 3 more authors.
Applied Microbiology and Biotechnology | Year: 2011

The disparity of secondary metabolites in Penicillium chrysogenum between two scales of penicillin G fermentation (50 L as pilot process and 150,000 L as industrial one) was investigated by ion-pair reversed-phase liquid chromatography tandemed with hybrid quadrupole time-of-flight mass spectrometry. In industrial process, the pools of intracellular L-α-aminoadipyl-L- cysteinyl-D-valine (LLD-ACV) and isopenicillin N (IPN) were remarkably less than that in the pilot one, which indicated that the productivity of penicillin G might be higher in the large scale of fermentation. This conclusion was supported by the higher intracellular penicillin G concentration as well as its higher yield per unit biomass in industrial cultivation. The different changing tendencies of IPN, 6-aminopenicillanic acid and 6-oxopiperide-2-carboxylic acid between two processes also suggested the same conclusion. The higher content of intracellular LLD-ACV in pilot process lead to a similarly higher concentration of bis-δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine, which had an inhibitory effect on ACV synthetase and also subdued the activity of IPN synthetase. The interconversion of secondary metabolites and the influence they put on enzymes would intensify the discrepancy between two fermentations more largely. These findings provided new insight into the changes and regulation of secondary metabolites in P. chrysogenum under different fermentation sizes. © 2011 Springer-Verlag.


Qiao B.,Tianjin University | Lu H.,Tianjin University | Lu H.,Hebei Zhongrun Pharmaceutical Co. | Lu H.,Shijiazhuang Pharmaceutical Group Co. | And 4 more authors.
Engineering in Life Sciences | Year: 2013

Optimizing industrial-scale fermentation for Penicillium chrysogenum is of significance for increasing commercial production of antibiotics. Lipidomics could be a valuable tool for the investigation in the behaviors of P. chrysogenum in realistic industrial environments. In this work, the phospholipid (PL) profiles of an industrial strain of P. chrysogenum were compared in different scale processes. PL was performed on LC/ESI/MSn system. It was found that industrial P. chrysogenum cells absorbed significant amounts of exogenous saturated and (poly) unsaturated fatty acids (PUFAs) from feedstock and incorporated them into their cell membranes during two fermentations. Results showed that the PL species that contain the PUFAs, that is, linolenic acid and hexadecadienoic acid, were quite variable between pilot and industrial scales of fermentations. Higher levels of PUFA-containing PLs in rapid- and linear-growth stages during industrial fermentation implied the occurrence of dramatic variations in cell membrane fluidity during these periods. It was speculated that this behavior was due to impacts of multiple physical and chemical factors present in the fermentation environment during this large-scale fed-batch process. The identified PUFA-containing PLs could be used as valuable biomarkers for optimizing industrial-scale fermentation for P. chrysogenum. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Cheng J.-S.,Tianjin University | Zhao Y.,Tianjin University | Qiao B.,Tianjin University | Lu H.,Tianjin University | And 5 more authors.
Applied Biochemistry and Biotechnology | Year: 2016

The intracellular proteomes of the Penicillium chrysogenum throughout pilot and industrial processes were investigated by using 2-DE combined with MALDI-TOF-TOF MS, respectively. We detected a total of 223 spots corresponding to 154 proteins and 231 spots corresponding to 157 proteins throughout pilot and industrial processes, respectively. The levels of glyceraldehyde-3-phosphate dehydrogenase increased (5.1- and 2.5-fold) under the pilot process, while its levels were no significant changes under the industrial process at 140 and 170 h when compared with that at 2 h. The levels of isocitrate lyase and fumarate hydratase were increased significantly under the industrial process, while their levels had no obvious changes after 20 h of fermentation throughout the pilot process. These results indicate that there were remarkable differences in carbohydrate metabolism (including glycolysis, gluconeogenesis, pentose phosphate pathway, and tricarboxylic acid cycle) of P. chrysogenum during the pilot and industrial fermentations, which likely result in alterations of the primary metabolism and penicillin biosynthesis. Moreover, the differences in the levels of proteins involved in amino acid metabolisms (including valine, cysteine, and α-aminoadipic acid biosynthesis) indicated that the pilot and industrial processes influenced the supplies of penicillin precursors. Compared with that at 2 h, the maximum levels of superoxide (6.9-fold, at 32 h) and catalase (9-fold, at 80 h) during the industrial process and the maximum levels of superoxide (1.2-fold, at 20 h) and catalase (7.7-fold at 128 h) during the pilot process revealed the significant difference in cell redox homeostasis and stress responses during scale-up fermentation. Particularly, 10 spots corresponding to isopenicillin N synthetase and 4 spots corresponding to isopenicillin N (IPN) acyltransferase in pilot and industrial processes were identified, respectively. The levels of IPN acyltransferase (spots 197 and 198) and CoA ligase at 80 h during the industrial process were around 2-fold of that during the pilot process, indicating that the industrial process with a higher penicillin production per cell might provide available environments to induce over-expression of IPN acyltransferase and accelerate penicillin formation. These results provide new insights into the globally potential responses of P. chrysogenum to variations of environments in different fermentation scales so as to consequently regulate the penicillin production. © 2016 Springer Science+Business Media New York


Zhang L.,Chinese University of Hong Kong | Zhang L.,Hebei Medical University | Lu L.,Sun Yat Sen University | Chan W.M.,Chinese University of Hong Kong | And 3 more authors.
Neurochemical Research | Year: 2012

3-n-Butylphthalide (NBP) is a compound extracted from Chinese celery and is used as an antihypertensive herbal medicine for treating stroke patients. The aim of this study is to demonstrate the effects and mechanisms of this compound through in vitro and in vivo experiments. Culture experiments were performed by adding hydrogen peroxide (H 2O 2) to SH-SY5Y cells. From the MTT assay result, enhanced cell survival was observed with DL-NBP treatment, regardless of whether they are added before, simultaneously with or after the addition of H 2O 2. For the in vivo experiment, Spontaneously Hypertensive rats and Wistar Kyoto control rats with chronic cerebral ischemia, which were induced by bilateral transection of the common carotid arteries, were given DL-NBP. Their performances in the place navigation test and spatial probe test in the Morris Water Maze have significantly improved compared with the DL-NBP untreated animals, indicating an improvement in spatial learning and memory in the ischemic-animals. In addition, in the chick embryonic chorioallantoic membrane assay, angiogenesis was more vigorous under the effects of DL-NBP, together with increased expression of growth factors, VEGF, VEGF-receptor and bFGF. All these suggested that one of the mechanisms of DL-NBP might be ameliorating vascular dementia and promoting angiogenesis. © Springer Science+Business Media, LLC 2012.


Shang Z.,Hebei University of Science and Technology | Xu L.,Hebei University of Science and Technology | Zheng L.,Shijiazhuang Pharmaceutical Group Co. | Zhang Y.,Hebei University of Science and Technology
Acta Crystallographica Section E: Structure Reports Online | Year: 2012

In the title compound, C26H31NO3, the octahydro-1H-isoindole ring is not planar and the two rings are twisted with a C - C - C - C torsion angle of 73.6 (4)°. The six-membered ring has a chair conformation while the five-membered ring has an envelope conformation on the C-atom in position 7a. The H atoms in the 3a- and 7a-psitions are cis and the H - C - C - H torsion angle is 42.36°.


Wang J.-X.,Hebei University of Science and Technology | Wang P.,Hebei University of Science and Technology | Qi S.,Shijiazhuang Pharmaceutical Group Co. | Liu L.-Y.,Shijiazhuang Pharmaceutical Group Co. | Shang Z.-H.,Hebei University of Science and Technology
Chinese Journal of New Drugs | Year: 2014

Objective: To optimize the current synthesis routes for developing a new synthetic route for mitiglinide calcium production. Methods: (S)-2-benzylsuccinic acid and CDI were used as the starting materials to get the active amide. Then the active amide was reacted with the hydrochloride salt of cis-hexahydroisoindoline and benzyl chloride to get purified benzyl ester; thereafter, debenzylation and calcification were done to get mitiglinide calcium. Results: Mitiglinide calcium was synthesized with a total yield of 24.46%, and the purity was >99.88% determined by HPLC. Conclusion: This synthetic process is easy to operate with high yield and purity, and suitable for industrial production.


Shang Z.,Hebei University of Science and Technology | Tao X.,Hebei University of Science and Technology | Ha J.,Shijiazhuang Pharmaceutical Group Co. | Yu F.,Shijiazhuang Center Hospital
Acta Crystallographica Section E: Structure Reports Online | Year: 2012

The title pyrimidine derivative, C18H21N 3O6, was obtained by the reaction of methyl 2-[2-(benzyloxycarbonyl)aminopropan-2-yl]-5-hydroxy-6-oxo-1,6-dihydropyrimidine- 4-carboxylate with dimethyl sulfate in dimethyl sulfoxide. The molecule has a V-shaped structure, the phenyl and the pyrimidine rings making a dihedral angle of 43.1(1)°. The methyl group substituting the pyrimidine ring deviates slightly from the ring mean-plane [C-N-C-C torsion angle = 5.49(15)°], and the methyl ester substituent has a conformation suitable for the formation of an intramolecular O-H⋯O hydrogen bond with the hydroxyl functionality. In the crystal, molecules are linked into chains along the b axis by N-H⋯O hydrogen bonds.

Loading Shijiazhuang Pharmaceutical Group Co. collaborators
Loading Shijiazhuang Pharmaceutical Group Co. collaborators