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Use of plant enzymes in bacterial cell factories may lead to effective anti-cancer drugs.
Scientists have developed a novel method that produces specialized enzymes in bacterial cell factories. These compounds can be used as active ingredients in anti-cancer drugs.
P450 enzymes are a type of cytochrome used by plants to protect itself from predators and microbes.
Although P450s are considered one of the most important enzyme families in biosynthesis of plant-derived medicinal compounds, their hydrophobic nature makes it a challenge to use their robust cell factories.
In a study published by Biotechnology and Bioengineering, the investigators developed a toolbox that allows the plant proteins to produce these compounds and be recognized by the bacterial molecular machinery.
“The aim is to use bacteria because they are capable of growing rapidly in controlled fermenters, allowing us to produce large quantities of the enzymes,” the authors wrote.
For the study, the investigators modified and transferred P450 genes from plants to Escherichia coli bacteria to achieve these results, and to examine whether the microbes could produce larger quantities of the P450 enzymes than current methods.
“For the bacteria to properly express the enzymes, the corresponding DNA sequence must frequently be modified to facilitate ‘decoding’ by the bacteria’s system,” said lead author Darío Vázquez-Albacete.
The investigators created a toolbox of auxiliary DNA sequences, which were allowed to express approximately 50 P450 enzymes from different plants in E. coli.
Plants generate various compounds to protect against dehydration, the sun, and predators.
“Many of these are synthesized by P450s, whose function is still very little understood, so there is enormous potential to discover new compounds,” the authors noted.
Additionally, some of P450 enzymes are involved in synthesizing ingenol, which is used to treat psoriasis and is manufactured using traditional chemical techniques, while others are used to produce the anti-cancer drug Taxol.