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Turning Bacteria into Factories Producing Cancer Drugs

Bacterial cells have been turned into little factories that produce cancer drugs. The new findings documenting the technique used to transform bacteria into drug-making machines are published in the journal Biotechnology and Bioengineering.

E. coli bacteria, producing P450, bound to green fluorescent protein. Photo credits: DTU.

A team of researchers from the Novo Nordisk Foundation Center for Biosustainability of Danmarks Tekniske Universitet (DTU) has modified bacterial species E. coli to produce P450 enzymes—the latter are normally synthesised by plants as protection against microbes and predators, and are used in the making of cancer drugs. The aim of turning E. coli, instead of plants, into drug factories is to generate greater yields of the enzymes.

Study lead author, Darío Vázquez-Albacete, explains the limitations of using plants to make the P450 enzymes: plants produce them in very small amounts, and the extraction process that would be required to harvest it would be too complex. Furthermore, this would need chemical synthesis processes that are deemed polluting because of the presence of oil derivatives. Moreover, plant species which make cancer drug Taxol, namely the yew, are endangered. Bacteria, on the other hand, display rapid growth in controlled fermenters, which would result in large amounts of the enzymes being produced.

P450 is a specialised enzyme involved in the synthesis of chemical compounds spanning over a range of functions in plants. One of these uses includes defense against predators like herbivores, insects and microbes. Scientists also use it to biosynthesise cancer drugs.

“These powerful compounds can be used as active ingredients in drugs for treating diseases such as cancer and psoriasis,” says Vázquez-Albacete.

The team developed tools to incorporate the specific plant proteins (involved in the making of the desired compounds) into bacterial machinery. P450 genes from plants were first modified and transferred to E. coli to verify whether the latter were able to make larger quantities of the enzymes. It was found that the bacteria would use the information from the DNA to express the enzymes when the corresponding DNA sequence was constantly changed to ease the process of decoding by the bacteria.

The results show that the bacteria, when fed with ‘auxiliary’ DNA sequences, expressed around 50 different P450 enzymes obtained from different plants. A group of these enzymes are involved in the synthesis of compound ingenol used in the treatment of psoriasis, and yet others, in the production of cancer drug Taxol.

The new findings might also pave the way for the identification of new compounds, explains the author. According to the researchers, plants use P450 to make a number of compounds whose function is not yet fully understood, thus making space for potential discovery.


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