Taxol is the world's leading anti-cancer drug and has proven a significant effect on a variety of cancer since the 1970s. Its molecular structure and mechanism of function is very complex: studies in 1977 showed that paclitaxel could be incorporated into the cell's microtubule assembly, stabilize microtubules, and prevent shrinkage and chromosome segregation associated with the slowdown of cell division.
The researchers believe that metabolic engineering is the production of complex molecules, including drugs, health products, flavors and spices, which are the most promising approaches. Metabolic engineering can produce expected materials by changing the genetic and regulatory system of a single cell - essentially to converting existing cells into a small factory. Taxol is considered to be the most possible candidate of this biosynthetic pathway.
The research results published by an international research team in the PNAS (Proceedings of the National Academy of Sciences) are committed to overcome existing obstacles in metabolic engineering and select a specific precursor Taxol as their target.
An international research team recently published study in on the metabolic engineering is committed to overcoming the existing obstacles, and select a specific pre-paclitaxel body as its goal. Taking into account the new types of chemical metabolic processes including polymerization and cyclization, glycosylation, they tried to use the cytochrome P450 enzymes in Escherichia coli - a high level of oxygenation chemistry to systematic - nature is usually used for molecular oxidation.
Cells use a particular system to construct complex molecules. First, they build bracket by polymerization and cyclization basal metabolic components. Once the stent in place, cut with a portion of the enzyme functional groups modified molecule - basically, the only part of the molecule works - and these functional processes have a hierarchy in oxygenation, which is mediated by the enzyme P450, also very important. P450 is widely present in the natural metabolic chemistry, because it has no selective oxygenation unique ability of activated carbon, which makes it particularly suitable for the synthesis of molecular biology field.
The researchers did not attempt to produce Taxol, because this is a difficult task. Instead, they tried the drug biosynthesis third step systematic. They designed the P450-mediated catalysis in E. coli, and the first time proved that the bacterium is a suitable host plant of cytochrome P450. They wrote, "Ultimately, this work promoted paclitaxel metabolic engineering, and in the past five years the project has been at a standstill."
They also found that high expression of a single passage upstream module can affect the expression of the enzyme, which in turn undermine the overall performance of their molecular systems. Although the exact cause is unknown, they speculate that this may be the results of some resources were exclusive for the P450 enzymes in the later stage. They wrote, "Fully articulated Taxol pathway had not been completed and it appears to be more complex than previously thought. This work laid faster foundation with more efficient expression for P450 enzymes in E. coli. We hope that in the near future, we will see large-scale application of complex biological compounds and valuable natural product."
Read more: http://www.cusabio.com/Polyclonal-Antibody/SLC34A2-Antibody-HRP-conjugated-11106193.html
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