Scientists have been interested in using bacteria as engineered factories that are capable of making specialized substances that may also be difficult or expensive to obtain or produce. Researchers have now turned to bacteria to make cytochrome P450 enzymes. These enzymes are critical to the metabolism of foreign compounds in humans and also have important roles in both plant and bacterial cells. The work has been published in Biotechnology and Bioengineering.
"These powerful compounds can be used as active ingredients in drugs for treating diseases such as cancer and psoriasis," commented lead author Darío Vázquez-Albacete. He performed the work at the Novo Nordisk Foundation Center for Biosustainability, which is managed by the Technical University of Denmark.
He stressed the diverse impact this work could have, on areas from the reducing harm to the environment and improving the production of cancer drugs. ”The new technique is a significant step forward, as plants produce P450 enzymes in very small amounts, extraction is very complex and sometimes we have to use polluting chemical synthesis processes which involve the use of oil derivatives. Additionally, some plant species such as the yew (Taxus baccata), from which the cancer drug Taxol is obtained, are endangered species,” said Vázquez-Albacete,
"We have developed tools which will allow the proteins from plants that produce these compounds to 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," explained Vázquez-Albacete.
The investigators took advantage of Escherichia coli, a well characterized bacterium, and altered it by adding plant P450 genes. The researchers found that the genome needed some special attention so the bacteria would understand the plant genes.
“In order 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 Vázquez-Albacete.
The research team has created an array of various DNA sequences that enables E.coli to synthesize about 50 different plant cytochrome P450 enzymes. Some of these P450 enzymes are involved in drug production Ingenol is used as a treatment for psoriasis, as mentioned some P450 are used to make a cancer drug called Taxol; P450 enzymes that can now be made by bacteria are used in the manufacture of those drugs.
The researcher noted that plants create many compounds that may be of interest to humans as they work to protect themselves from sun exposure, dehydration and other environmental challenges. "Many of these are synthesized by P450s, whose function is still very little understood, so there is enormous potential to discover new compounds.”
There are many substances that engineers and scientists have tried to make with bacteria, one example is biodegradable plastic. Learn more from the video.