GM-yeast used as BIA biofactories

By Nick Taylor

- Last updated on GMT

Related tags: Bacteria, Enzyme

Researchers claim to have facilitated the development and manufacture of a wide range of alkaloids using genetically modified yeast.

The research published in an advance online edition of Nature Chemical Biology ​states that by inserting plant genes into yeast cells synthesis pathways were altered to produce a range of benzylisoquinoline alkaloids (BIAs).

BIAs are a diverse range of metabolites that are known to have pharmacological potential in treating ailments including cancer, hypertension and autoimmune disorders.

However, until now there has been no efficient method of extracting significant quantities of BIAs, which is what prompted the researchers to investigate yeast.

The researchers wrote: “Our engineered microbial hosts offer access to a rich group of BIA molecules and associated activities that will be further expanded through synthetic chemistry and biology approaches​.”

By inserting genes from three plants, the opium poppy, common meadow rue and thale cress, into yeast cells the inner workings were modified to produce BIAs.

The gene for human enzyme P450 was also inserted and by varying the enzymatic composition of the yeast cell the researchers produced seven different BIAs.

By further modifying the yeast cell the researchers claim that it will be possible to produce a wider spectrum of BIAs from simpler substrates.

There is also the possibility of using combinations of enzymes that do not occur naturally to produce novel BIAs that have never previously been synthesised.

All seven of the BIAs synthesised in the research are already produced by plants but their complexity and the fact that they only accumulate in small quantities prevents efficient harvesting.

The researchers obtained yields of 100 to 200mg per litre, which they believe to be adequate. However, they added that this could be increased by up to 100 fold for commercial production by optimising the fermentation process.

By modifying the yeast cells to manufacture the optimum quantity of each enzyme in the synthesis pathway the researchers believe they have created a highly efficient production system.

The researchers acknowledge that considerably more research is necessary to develop the system to a commercial level.

However, with thousands of BIAs already known and the ability to create novel compounds the system’s considerable potential should ensure it gets the necessary attention.

Related topics: Ingredients, Processing equipment

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