From pharma foe to meds making friend: E.coli changes its ways

Traditionally, glycoproteins – both those used in the production of drugs like erythropoietin (EPO) and in receptor research – have been manufactured in small amounts using complicated eukaryotic cell systems, like the Chinese Hamster Ovary (CHO) line.

Such eukaryotic cultures are time consuming to establish, expensive to maintain and susceptible to viral contamination, which can be a costly problem to solve as a number of high profile manufacturers can attest.​ As a result, glycoproteins can be expensive to produce.

Now however scientists at Cornell University in New York, US think they have found a way of overcoming some of these hurdles using a genetically modified strain of E.coli​ and a process known as bottom up glycoengineering, or BUG

How it works​

The Cornell team introduced a number of enzymes derived from yeast into a strain of E.coli​ giving it the ability to synthesize glycan, which is the core structure of all glycoproteins and not something that prokaryotic bacteria can otherwise produce.

They also introduced an enzyme from the bacteria Campylobacter jejuni into the E.coli strain, enabling the organism to combine the glycan cores with other proteins to produce the desired glycoproteins.

Matthew DeLisa - a researcher on the paper 'An engineered eukaryotic protein glycosylation pathway in Escherichia coli' - told in-PharmaTechnologist.com: “We have engineered E. coli cells that can produce a five-carbohydrate chain - the ‘core structure’ of the eukaryotic carbohydrate sequence - that can be further attached to several eukaryotic proteins made in the same cell.”​

“Such a feat had never previously been accomplished” he continued, ​adding that it has​ “immediate importance for industrial production of glycoproteins that scientists use in looking for therapies for various diseases.​

“The pharmaceutical industry could benefit in several ways, not the least of which is the ability to make glycoproteins quickly and affordably for drug discovery or manufacturing.”​

DeLisa added the BUG approach can also allow custom design of glycoprotein drugs for the first time ever. “This is not possible in any other existing or emerging technology,”​ he said.

When asked about the limits of the tech – which is being commercialised by the startup company Glycobia - DeLisa said although it only useful for one particular class of drug the team believes they will be able to synthesize many different drugs within the class.

“Perhaps we will be able to introduce newer and better drugs that fall into this class, as well,”​ he added.