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Liu R.,Wuhan University | Liu R.,Wuhan J1 Biotech Co. | Zhu F.,Wuhan University | Lu L.,Wuhan University | And 6 more authors.
Metabolic Engineering | Year: 2014

Fatty alcohols are important components of surfactants and cosmetic products. The production of fatty alcohols from sustainable resources using microbial fermentation could reduce dependence on fossil fuels and greenhouse gas emission. However, the industrialization of this process has been hampered by the current low yield and productivity of this synthetic pathway. As a result of metabolic engineering strategies, an Escherichia coli mutant containing Synechococcus elongatus fatty acyl-ACP reductase showed improved yield and productivity. Proteomics analysis and in vitro enzymatic assays showed that endogenous E. coli AdhP is a major contributor to the reduction of fatty aldehydes to fatty alcohols. Both in vitro and in vivo results clearly demonstrated that the activity and expression level of fatty acyl-CoA/ACP reductase is the rate-limiting step in the current protocol. In 2.5-L fed-batch fermentation with glycerol as the only carbon source, the most productive E. coli mutant produced 0.75. g/L fatty alcohols (0.02. g fatty alcohol/g glycerol) with a productivity of up to 0.06. g/L/h. This investigation establishes a promising synthetic pathway for industrial microbial production of fatty alcohols. © 2013 International Metabolic Engineering Society.


Chen H.,Huazhong University of Science and Technology | Li J.,Wuhan University | Jiao L.,Huazhong University of Science and Technology | Petersen R.B.,Case Western Reserve University | And 4 more authors.
Journal of Physiology | Year: 2014

Diabetic nephropathy is the primary cause of end-stage renal disease. Increasing numbers of patients are suffering from this disease and therefore novel medications and therapeutic approaches are urgently needed. Here, we investigated whether apelin-13, the most active member of the adipokine apelin group, could effectively suppress the development of nephropathy in Akita mouse, a spontaneous type 1 diabetic model. Apelin-13 treatment decreased diabetes-induced glomerular filtration rate, proteinuria, glomerular hypertrophy, mesangial expansion and renal inflammation. The inflammatory factors, activation of NF-κB, histone acetylation and the enzymes involved in histone acetylation were further examined in diabetic kidneys and high glucose- or sodium butyrate-treated mesangial cells in the presence or absence of apelin-13. Apelin-13 treatment inhibited diabetes-, high glucose- and NaB-induced elevation of inflammatory factors, and histone hyperacetylation by upregulation of histone deacetylase 1. Furthermore, overexpression of apelin in mesangial cells induced histone deacetylation under high glucose condition. Thus, apelin-13 may be a novel therapeutic candidate for treatment of diabetic nephropathy via regulation of histone acetylation. © 2013 The Physiological Society.


Wang L.-L.,Wuhan University | Sun Y.,Wuhan University | Huang K.,Huazhong University of Science and Technology | Huang K.,Wuhan Institute of Biotechnology | Zheng L.,Wuhan University
Molecular Nutrition and Food Research | Year: 2013

Curcumin, the major extraction of turmeric, has been widely used in many countries for centuries both as a spice and as a medicine. In the last decade, researchers have found the beneficial effects of curcumin on multiple disorders are due to its antioxidative, anti-inflammatory, and antiproliferative properties, as well as its novel function as an inhibitor of histone aectyltransferases. In this review, we summarize the recent progress made on studying the beneficial effects of curcumin on multiple retinal diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration. Recent clinical trials on the effectiveness of phosphatidylcholine formulated curcumin in treating eye diseases have also shown promising results, making curcumin a potent therapeutic drug candidate for inflammatory and degenerative retinal and eye diseases. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Guo D.,Wuhan University | Guo D.,Wuhan Institute of Biotechnology | Zhu J.,Wuhan University | Deng Z.,Wuhan University | And 3 more authors.
Metabolic Engineering | Year: 2014

Fatty acid short-chain esters (FASEs) are biodiesels that are renewable, nontoxic, and biodegradable biofuels. A novel approach for the biosynthesis of FASEs has been developed using metabolically-engineered E. coli through combination of the fatty acid and 2-keto acid pathways. Several genetic engineering strategies were also developed to increase fatty acyl-CoA availability to improve FASEs production. Fed-batch cultivation of the engineered E. coli resulted in a titer of 1008. mg/L FASEs. Since the fatty acid and 2-keto acid pathways are native microbial synthesis pathways, this strategy can be implemented in a variety of microorganisms to produce various FASEs from cheap and readily-available, renewable, raw materials such as sugars and cellulose in the future. © 2014 International Metabolic Engineering Society.


Li Y.,Wuhan Institute of Biotechnology | Cui R.,Wuhan University | Zhang P.,Wuhan Institute of Biotechnology | Chen B.-B.,Wuhan Institute of Biotechnology | And 5 more authors.
ACS Nano | Year: 2013

Microbial cells have shown a great potential to biosynthesize inorganic nanoparticles within their orderly regulated intracellular environment. However, very little is known about the mechanism of nanoparticle biosynthesis. Therefore, it is difficult to control intracellular synthesis through the manipulation of biological processes. Here, we present a mechanism-oriented strategy for controlling the biosynthesis of fluorescent CdSe quantum dots (QDs) by means of metabolic engineering in yeast cells. Using genetic techniques, we demonstrated that the glutathione metabolic pathway controls the intracellular CdSe QD formation. Inspired from this mechanism, the controllability of CdSe QD yield was realized through engineering the glutathione metabolism in genetically modified yeast cells. The yeast cells were homogeneously transformed into more efficient cell-factories at the single-cell level, providing a specific way to direct the cellular metabolism toward CdSe QD formation. This work could provide the foundation for the future development of nanomaterial biosynthesis. © 2013 American Chemical Society.


Huang J.,Hubei University | Wan D.,Hubei University | Li J.,Hubei University | Chen H.,Huazhong University of Science and Technology | And 4 more authors.
Epigenetics | Year: 2015

Kidney diseases, including chronic kidney disease (CKD) and acute kidney injury (AKI), are associated with inflammation. The mechanism that regulates inflammation in these renal injuries remains unclear. Here, we demonstrated that p300/CBP-associated factor (PCAF), a histone acetyltransferase, was overexpressed in the kidneys of db/db mice and lipopolysaccharide (LPS)-injected mice. Moreover, elevated histone acetylation, such as H3K18ac, and up-regulation of some inflammatory genes, such as ICAM-1, VCAM-1, and MCP-1, were found upon these renal injuries. Furthermore, increased H3K18ac was recruited to the promoters of ICAM-1, VCAM-1, and MCP-1 in the kidneys of LPS-injected mice. In vitro studies demonstrated that PCAF knockdown in human renal proximal tubule epithelial cells (HK-2) led to downregulation of inflammatory molecules, including VCAM-1, ICAM-1, p50 subunit of NF-κB (p50), and MCP-1 mRNA and protein levels, together with significantly decreased H3K18ac level. Consistent with these, overexpression of PCAF enhanced the expression of inflammatory molecules. Furthermore, PCAF deficiency reduced palmitate-induced recruitment of H3K18ac on the promoters of ICAM-1 and MCP-1, as well as inhibited palmitate-induced upregulation of these inflammatory molecules. In summary, the present work demonstrates that PCAF plays an essential role in the regulation of inflammatory molecules through H3K18ac, which provides a potential therapeutic target for inflammation-related renal diseases. © 2015 Taylor & Francis Group, LLC.


Zhou C.-H.,Wuhan University | Long Y.-M.,Wuhan Institute of Biotechnology | Qi B.-P.,Wuhan Institute of Biotechnology | Pang D.-W.,Wuhan Institute of Biotechnology | Zhang Z.-L.,Wuhan Institute of Biotechnology
Electrochemistry Communications | Year: 2013

A novel electrochemical immunosensor based on the integration of immunomagnetic separation and bienzymatic amplification for sensitive detection of virus particles was fabricated in this work. The bienzymatic strategy was realized by using the first enzyme as tracer tagged on immunomagnetic beads which could be accumulated on the magneto controlled home-made Au electrode (m-AuE) and the second enzyme immobilized on the m-AuE by layer-by-layer (LBL) assembly technique. The proposed immunosensor not only provides a rapid, simple, cost-effective and on-site platform with high sensitivity, selectivity, and reproducibility for early diagnosis but also presents a new approach for sensitive magneto immunoassay. © 2013 Elsevier B.V.


Li Y.,Huazhong University of Science and Technology | Yan J.,Huazhong University of Science and Technology | Zhang X.,Huazhong University of Science and Technology | Huang K.,Huazhong University of Science and Technology | Huang K.,Wuhan Institute of Biotechnology
Proteins: Structure, Function and Bioinformatics | Year: 2013

More than 20 human diseases, including Alzheimer's disease, Parkinson's disease, and prion disease, originate from the deposition of misfolded proteins. These proteins, referred as amyloidogenic proteins, adopt a β-sheet-rich structure when transformed from soluble state into insoluble amyloid fibrils. Amyloid formation is influenced by a number of factors that affect the intermolecular interaction, including pH, temperature, ion strength, and chemical bonds. In this review, we focus on the role of disulfide on the stability, structure, oligomerization, and amyloidogenecity of native folded or unfolded amyloidogenic proteins. The effects of introduced disulfide bonds on the amyloidogenicity of proteins lacking native disulfide are also reviewed. © 2013 Wiley Periodicals, Inc.


Huang L.,Huazhong University of Science and Technology | Liu X.,Huazhong University of Science and Technology | Cheng B.,Central Hospital of Wuhan | Huang K.,Huazhong University of Science and Technology | Huang K.,Wuhan Institute of Biotechnology
Archives of Biochemistry and Biophysics | Year: 2015

The process of protein aggregation from soluble amyloidogenic proteins to insoluble amyloid fibrils plays significant roles in the onset of over 30 human amyloidogenic diseases, such as Prion disease, Alzheimer's disease and type 2 diabetes mellitus. Amyloid deposits are commonly found in patients suffered from amyloidosis; however, such deposits are rarely seen in healthy individuals, which may be largely attributed to the self-regulation in vivo. A vast number of physiological factors have been demonstrated to directly affect the process of amyloid formation in vivo. In this review, physiological factors that influence amyloidosis, including biological factors (chaperones, natural antibodies, enzymes, lipids and saccharides) and physicochemical factors (metal ions, pH environment, crowding and pressure, etc.), together with the mechanisms underlying these proteostasis effects, are summarized. © 2015 Elsevier Inc.


Liu X.,Huazhong University of Science and Technology | Gong H.,Huazhong University of Science and Technology | Huang K.,Huazhong University of Science and Technology | Huang K.,Wuhan Institute of Biotechnology
Cancer Science | Year: 2013

The kinesin superfamily (KIF) is a group of proteins that share a highly conserved motor domain. Except for some members, many KIF proteins have adenosine triphosphatase activity and microtubule-dependent plus-end motion ability. Kinesins participate in several essential cellular functions, including mitosis, meiosis and the transport of macromolecules. Increasing evidence indicates kinesin proteins play critical roles in the genesis and development of human cancers. Some kinesin proteins are associated with maligancy as well as drug resistance of solid tumor. Thus, targeting KIF therapy seems to be a promising anticancer strategy. Inhibitors of KIF such as kinesin spindle protein (KSP/Eg5) have entered clinical trials for monotherapy or in combination with other drugs, and kinesins other than Eg5 with various potential anticancer target characteristics are also constantly being discovered and studied. Here, we summarize the oncogenic roles of kinesin proteins and potential cancer therapy strategies that target KIF. © 2013 © 2013 Japanese Cancer Association.

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