PNAS:Escherichia coli into drug factories


Taxol is a world famous cancer drug, has been shown in the 1970 of the 20th century, has a significant effect on many types of cancer.It is a natural substance from yew bark, because of this, its molecular structure is very complex, its mechanism as such: in 1977, the study showed that taxol can be combined into a cell Assembly of microtubules, and stabilizing the microtubules, which prevent shrinkage and prevent associated with chromosome segregation in cell division slows down.


Since it is a natural source to synthetic paclitaxel supply initially was limited;Later researchers have figured out how to in the private sector from the common precursor of extracting taxol from yew and chemical synthesis to produce the drug.At present, the Bristol-Myers Squibb Company used taxol production by cell culture.


Focus on the future, researchers say, metabolic engineering is the production of complex molecules, including pharmaceuticals, health care products, flavor and fragrance, the most promising approach.Metabolic engineering can change single cell genetic and regulatory system to produce the desired material--essentially transform existing cells into small factories.Biosynthesis of taxol is considered to be the way most likely candidate.


An international research team, published recently in the United States National Academy (Proceedings of the National Academy of Sciences) on the results committed to overcome some of the existing obstacles in the metabolic engineering, and choose a specific precursor of taxol as their goal.Taking into account the new types of metabolic chemical processes including polymerization, ring and glycosylation, they tried to use in the Escherichia coli cytochrome P450 enzymes in nature are often used in molecular chemical oxidation-systematic high levels of oxygenation.


Cells using a specific system to construct complex molecules.First of all, through aggregation and cyclic basal metabolic component to build support.Once the stent is in place, cutting enzyme used part of the faculty to modify elements-basically, just part of the work in molecular-and these procedures there is a hierarchy in the oxygenation, which is mediated by P450 enzymes, it is also very important.P450 metabolic chemistry of pepsin, selective oxygenation without activated carbon because it has unique abilities, which makes it particularly suitable for the field of molecular biology.


Researchers did not attempt to produce taxol, this is a difficult task;Instead, they tried to systematize the third step in the biosynthesis of drugs.They designed a P450-mediated Catalysis in Escherichia coli, and for the first time, the bacteria is a suitable host plant cytochrome P450.They wrote, "in the end, this work promotes the metabolic engineering of taxol, and over the past five years, the project has been at a standstill. ”


They also found that single channel module expression expression will affect upstream, thereby undermining their overall system performance.Although the exact cause is unknown, but they speculate that the late it may be exclusive of P450 enzymes in the results of some of the resources required.They wrote, "explain fully the taxol means work is not yet complete, and more complex than previously thought.. ...... This work laid the P450 enzyme in Escherichia coli in the faster, more efficient expression based, I hope soon we will see the biosynthesis of complex and large scale application of valuable natural products. ”


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