Establishment of a novel anabolism-based addiction system with an artificially introduced mevalonate pathway: Complete stabilization of plasmids as universal application in white biotechnology

2009 ◽  
Vol 11 (3) ◽  
pp. 168-177 ◽  
Author(s):  
Jens Kroll ◽  
Anna Steinle ◽  
Rudolf Reichelt ◽  
Christian Ewering ◽  
Alexander Steinbüchel
Keyword(s):  
Mevalonate Pathway ◽  
White Biotechnology ◽  
Universal Application

A Systems Approach to ER Stress Pathway Dynamics Reveals the Impact of Freeze-Dried Broccoli Extract to Mitigate Inflammation in Human Adipocytes through the Mevalonate Pathway

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2076-P
Author(s):  
ALICE MURPHY ◽  
SAHAR AZHARIAN ◽  
GYANENDRA TRIPATHI ◽  
GUY BARKER ◽  
MICHAEL J. CHAPPELL ◽  
...  
Keyword(s):  
Er Stress ◽  
Systems Approach ◽  
Mevalonate Pathway ◽  
Human Adipocytes ◽  
Freeze Dried ◽  
The Impact ◽  
Stress Pathway

Isotopically Labeled Desthiobiotin Azide (isoDTB) Tags Enable Global Profiling of the Bacterial Cysteinome

2019 ◽  
Author(s):  
Patrick R. A. Zanon ◽  
Lisa Lewald ◽  
Stephan M. Hacker
Keyword(s):  
Binding Sites ◽  
Bacterial Resistance ◽  
Mevalonate Pathway ◽  
Rapid Development ◽  
High Reactivity ◽  
Functional Importance ◽  
Essential Proteins ◽  
Covalent Inhibitors ◽  
Druggable Targets ◽  
Covalent Ligands

Rapid development of bacterial resistance has led to an urgent need to find new druggable targets for antibiotics. In this context, residue-specific chemoproteomic approaches enable proteome-wide identification of binding sites for covalent inhibitors. Here, we describe isotopically labeled desthiobiotin azide (isoDTB) tags that are easily synthesized, shorten the chemoproteomic workflow and allow an increased coverage of cysteines in bacterial systems. We quantify 59% of all cysteines in essential proteins in <i>Staphylococcus aureus</i> and discover 88 cysteines with high reactivity, which correlates with functional importance. Furthermore, we identify 268 cysteines that are engaged by covalent ligands. We verify inhibition of HMG-CoA synthase, which will allow addressing the bacterial mevalonate pathway through a new target. Overall, a comprehensive map of the bacterial cysteinome is obtained, which will facilitate the development of antibiotics with novel modes-of-action.

A generic method of design of on-site stormwater detention storages

1995 ◽  
Vol 32 (1) ◽  
pp. 93-99 ◽  
Author(s):  
Donald Ian Phillips
Keyword(s):  
Design Theory ◽  
Drainage System ◽  
Entire Length ◽  
Community Assets ◽  
Drainage Design ◽  
Urban Consolidation ◽  
Universal Application ◽  
Method Of Design

On-site stormwater detention is widely used in Australia as a means of controlling the increased storm discharges from urban consolidation projects. However, unless the maximum permissible site discharge is correctly determined, the local piped drainage system may be overloaded. This paper presents a generic methodology that integrates detention storage behaviour with drainage design theory in such a manner as to protect the entire length of the downstream drainage system. Its generic nature facilitates its universal application to all systems, protecting these valuable community assets throughout their service lives.

Statins as the Controlling Agents for Non-Hodgkin's Lymphomas via Increasing the Casein Kinase 2 Interacting Protein-1: A Hypothesis

2020 ◽  
Vol 17 (5) ◽  
pp. 616-618
Author(s):  
Kimia Kazemi ◽  
Negin Mozafari ◽  
Hajar Ashrafi ◽  
Pedram Rafiei ◽  
Amir Azadi
Keyword(s):  
Cell Proliferation ◽  
Mevalonate Pathway ◽  
Casein Kinase ◽  
Casein Kinase 2 ◽  
Interacting Protein ◽  
Akt Phosphorylation ◽  
Anticancer Properties ◽  
Proliferation And Apoptosis ◽  
Cellular Signaling Pathway ◽  
Hodgkin's Lymphomas

Background: Non-Hodgkin's lymphomas (NHL), derived from B- or T-cell, consist of a heterogeneous group of malignant lymphoproliferative disorders. Knockdown of Casein kinase 2 interacting protein-1 (CKIP-1) in NHL promoted cell proliferation and inhibited apoptosis via enhancing phosphorylated Protein Kinase B (PKB or AKT) expression. Statins are the class of drugs that inhibit the ratelimiting step of the mevalonate pathway, which is essential for the biosynthesis of various compounds, including cholesterol. Also, statins have anticancer properties being mediated by different mechanisms. Methods: A search on databases like Scopus and PubMed with keywords such as statin and non- Hodgkin's lymphomas was performed and Kyoto Encyclopedia of Genes and Genomes (KEGG) website was used to evaluate and reconfirm the involved cellular signaling pathway. Results: CKIP-1 is involved in the regulation of cell proliferation and apoptosis while plays an important role in many cancers. We can hypothesize that statins may increase the expression levels of CKIP-1 which could contribute to the reductions in phospho-AKT level. Hence, they may ameliorate the NHL patients via suppressing AKT phosphorylation and increasing CKIP- expression. Conclusion: Present review confirms the positive effect of statins on NHL by increasing CKIP-1 and reducing cell proliferation, subsequently.

Statins: A Conceivable Remedial Role for the Regulation of Cancer Progression

2019 ◽  
Vol 15 (2) ◽  
pp. 131-145
Author(s):  
Gajanan V. Sherbet
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Tumour Growth ◽  
Cell Function ◽  
Mevalonate Pathway ◽  
Biological Effects ◽  
Vegf Receptor ◽  
Mesenchymal Transition ◽  
Cancer Management ◽  
Metabolic Role

The mevalonate pathway (also known as the cholesterol biosynthesis pathway) plays a crucial metabolic role in normal cell function as well as in the pathological environment. It leads to the synthesis of sterol and non-sterol isoprenoid biomolecules which subserve a variety of cellular functions. It is known to be deregulated in many disease processes. Statins and bisphosphonates are prominent inhibitors of the mevalonate pathway. They inhibit cell proliferation and activate apoptotic signalling and suppress tumour growth. Statins subdue metastatic spread of tumours by virtue of their ability to suppress invasion and angiogenesis. The induction of autophagy is another feature of statin effects that could contribute to the suppression of metastasis. Herein highlighted are the major signalling systems that statins engage to generate these biological effects. Statins can constrain tumour growth by influencing the expression and function of growth factor and receptor systems. They may suppress epithelial mesenchymal transition with resultant inhibition of cell survival signalling, together with the inhibition of cancer stem cell generation, and their maintenance and expansion. They can suppress ER (oestrogen receptor)-α in breast cancer cells. Statins have been implicated in the activation of the serine/threonine protein kinase AMPK (5&#039; adenosine monophosphate-activated protein) leading to the suppression of cell proliferation. Both statins and bisphosphonates can suppress angiogenic signalling by HIF (hypoxia- inducible factor)-1/eNOS (endothelial nitric oxide synthase) and VEGF (vascular endothelial growth factor)/VEGFR (VEGF receptor). Statins have been linked with improvements in disease prognosis. Also attributed to them is the ability of cancer prevention and reduction of risk of some forms of cancer. The wide spectrum of cancer associated events which these mevalonate inhibitors appear to influence would suggest a conceivable role for them in cancer management. However, much deliberation is warranted in the design and planning of clinical trials, their scope and definition of endpoints, modes risk assessment and the accrual of benefits.

The Universal Rule of Law in the Thought of the Late Medieval Jurists of Roman and Canon Law

2018 ◽  
Author(s):  
Joseph Canning
Keyword(s):  
International Law ◽  
Rule Of Law ◽  
Canon Law ◽  
Research Question ◽  
Late Medieval ◽  
Legal Structure ◽  
Vertical Relationship ◽  
New Research ◽  
Universal Rule ◽  
Universal Application

Late medieval Roman and canon law jurisprudence provided the origins of European notions of a universal rule of law in two senses: a legal order of universal extent and a structure of higher norms of universal application. Whereas modern international law is primarily concerned with the horizontal relationship between states, medieval jurists mainly considered the vertical relationship between universal and territorial powers. They developed de iure–de facto arguments to justify a plurality of sovereign states within an overall universal legal structure. Contributions to the elaboration of theories of just war were also made. We must be cautious about claiming that late medieval jurists contributed to the development of early international law as normally understood. Nevertheless, early-modern theorists of international law referred back to the work of their medieval juristic predecessors. A new research question is emerging about the usefulness of using the term ‘international’ in interpreting medieval jurists.

scholarly journals Further engineering of R. toruloides for the production of terpenes from lignocellulosic biomass

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
James Kirby ◽  
Gina M. Geiselman ◽  
Junko Yaegashi ◽  
Joonhoon Kim ◽  
Xun Zhuang ◽  
...  
Keyword(s):  
Lignocellulosic Biomass ◽  
Copy Number ◽  
Mevalonate Pathway ◽  
Mevalonate Kinase ◽  
Metabolite Analysis ◽  
Lignocellulosic Hydrolysate ◽  
Microbial Conversion ◽  
Lignocellulosic Hydrolysates ◽  
Lignocellulosic Feedstocks ◽  
Fuels And Chemicals

Abstract Background Mitigation of climate change requires that new routes for the production of fuels and chemicals be as oil-independent as possible. The microbial conversion of lignocellulosic feedstocks into terpene-based biofuels and bioproducts represents one such route. This work builds upon previous demonstrations that the single-celled carotenogenic basidiomycete, Rhodosporidium toruloides, is a promising host for the production of terpenes from lignocellulosic hydrolysates. Results This study focuses on the optimization of production of the monoterpene 1,8-cineole and the sesquiterpene α-bisabolene in R. toruloides. The α-bisabolene titer attained in R. toruloides was found to be proportional to the copy number of the bisabolene synthase (BIS) expression cassette, which in turn influenced the expression level of several native mevalonate pathway genes. The addition of more copies of BIS under a stronger promoter resulted in production of α-bisabolene at 2.2 g/L from lignocellulosic hydrolysate in a 2-L fermenter. Production of 1,8-cineole was found to be limited by availability of the precursor geranylgeranyl pyrophosphate (GPP) and expression of an appropriate GPP synthase increased the monoterpene titer fourfold to 143 mg/L at bench scale. Targeted mevalonate pathway metabolite analysis suggested that 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR), mevalonate kinase (MK) and phosphomevalonate kinase (PMK) may be pathway bottlenecks are were therefore selected as targets for overexpression. Expression of HMGR, MK, and PMK orthologs and growth in an optimized lignocellulosic hydrolysate medium increased the 1,8-cineole titer an additional tenfold to 1.4 g/L. Expression of the same mevalonate pathway genes did not have as large an impact on α-bisabolene production, although the final titer was higher at 2.6 g/L. Furthermore, mevalonate pathway intermediates accumulated in the mevalonate-engineered strains, suggesting room for further improvement. Conclusions This work brings R. toruloides closer to being able to make industrially relevant quantities of terpene from lignocellulosic biomass.

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