A solitary archaeal compound can create a spectacular scope of regular and non-common cardiolipins

A solitary archaeal compound can create a spectacular scope of regular and non-common cardiolipins


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  • Source: University of Groningen

  • Date: 07 May,2021

Cells of all life forms are surrounded by a membrane that’s made of phospholipids. One of them are the cardiolipins, which form another class due to their distinctive structure.

When studying the enzyme that’s responsible for generating cardiolipins in archaea (single-cell organisms that constitute a separate domain of life), biochemists at the University of Groningen made a surprising discovery. A single archaeal enzyme can produce a spectacular assortment of natural and non-natural cardiolipins, as well as other phospholipids.

The results, which show potential for biotechnological applications, were published in the Journal of Biological Chemistry.

The phospholipids which are most abundant in cell membranes contain a hydrophilic head to which two hydrophobic tails are linked. Cardiolipins – so-called because they were first identified in cells – are slightly different as they are made up of a single head group that is attached to four lipid tails.

Odd head set
His interest in these types of cardiolipins stems from his job on a synthetic minimal cell. “Our group at the University of Groningen concentrates on cell membrane growth, dependent on the enzymatic production of fresh phospholipids from basic building blocks.”

Since cardiolipins exist in cell membranes of organisms from all domains of life, they are desired components of the synthetic cell. Exterkate wanted to know that enzymes are responsible for cardiolipin production in archaea.

The lipids that form the cell membrane of archaea are structurally different from those in the other two domains of life.”

Marten Exterkate, University of Groningen

“Additionally, while the other domain names have one dominant sort of cardiolipin, archaea seem to generate unique kinds of cardiolipins, with head groups which contain, as an example, just a single negative charge or various kinds of sugars or sulphate groups.

By searching the genomes of all archaeal species, Exterkate found several gene candidates for cardiolipin synthase.

“When we blended the receptor with potential building blocks, it generated the expected cardiolipin species. But then we noticed something really surprising: another cardiolipin with a very odd head set.” This turned out to be a molecule from the buffer solution in which the reaction took place.

“All the alarm bells started ringing,” Exterkate recalls. “If the receptor can incorporate this buffer molecule for a lipid head group, what else could it do?” As it turned out, the enzyme was able to create all sorts of variant cardiolipins and other phospholipids, including both natural and non-natural mind groups.

“Some enzymes are promiscuous; they can use slightly different variations of their regular substrates. However, this enzyme is promiscuous in the extreme.” It can produce lipids that, in bacterial cells, as an instance, require many diverse enzymes.

This is the first recognized enzyme having the ability to produce an whole assortment of different cardiolipins. Exterkate:

“Additional archaea have similar genes, which are likely also suited to producing different cardiolipins, indicating that the variety in archaeal cardiolipins could be synthesized by the same enzyme.” Aside from being a surprising discovery, the new enzyme could be interesting to the production of self-designed membranes.

This is beneficial because head groups in membrane phospholipids affect the general properties of the membrane and the use of enzymes that are incorporated in it. “The biotechnology industry could possibly use this receptor to artificially engineer membranes for specific purposes,” states Exterkate.

It’s becoming clear, though, that cardiolipins form a class of molecules. Exterkate and his colleagues suspect the receptor is involved in osmoregulation.

“Depending on the environment, the enzyme can switch the production towards different phospholipids and in doing this, alter the functionality of the membrane.”

The enzyme could also prove to be a bonus for the artificial cell that Exterkate and his colleagues are working on. “We planned to create a membrane using a minimalistic phospholipid composition, so we would not need to add lots of genes for various enzymes. Now, we can potentially produce a great deal of different phospholipids using just a single receptor”

Journal reference:

Exterkate, M., et al. (2021) A promiscuous archaeal cardiolipin synthase enables construction of diverse natural and unnatural phospholipids. Journal of Biological Chemistrydoi.org/10.1016/j.jbc.2021.100691.


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