Reconstructed Genes From The First Vertebrates Could Solve Manufacturing Challenges

E-coli have been injected with a reconstructed gene sequence from the first vertebrates and produced an enzyme that could be invaluable for chemical manufacturing. Science photos/Shutterstock

A genetic sequence that probably existed around the time the first vertebrates appeared has been reconstructed, and could prove exceptionally valuable for cheaper, more environmentally friendly chemical manufacturing.

When trying to modify complex molecules, conventional chemistry uses methods that “often attack multiple sites on a chemical, so one ends up with a mixture of by-products, while often requiring a lot of energy and creating harmful waste,” Professor Elizabeth Gillam of the University of Queensland said in a statement.

Living things use enzymes instead, and these have sometimes been put to work by chemists for their capacity to alter molecules in the desired places. Unfortunately, however, most enzymes are unstable, particularly above room temperature. For reactions that require even modestly high temperatures, these enzymes need to be replaced far too often to be useful.

CYP3s are a subgroup of P450 enzymes. Gillum told IFLScience they protect the body against fat-soluble toxic chemicals. By adding an oxygen atom to these chemicals, CYP3s make them water soluble and therefore easy for the body to excrete.

P450s are Gillam's specialty, and she told IFLScience that "most enzymes are quite specific,” targeting only a few, or one, molecules. However, CYP3s are not like this at all. The fact that CYP3s can make a wide range of molecules water soluble makes them potentially very valuable to industry, particularly pharmaceutical manufacturing. Unfortunately, existing versions of CYP3s break down quickly above 30ºC (86ºF).

Gillam reasoned this may not always have been the case, however. Hundreds of millions of years ago, life survived in oceans thought to average 60ºC (140ºF). Despite the simplicity of the era's lifeforms, the existence of P450s in all animals (and even plants and most bacteria) indicate they probably date back to this time.

Gillam is senior author of a paper in Nature Catalysis describing the reconstruction of the gene sequence that produced CYP3 in the first vertebrates. Although it is impossible to know the exact sequence of something that has been extinct for so long, Gillam and co-authors compared the sequences of a wide variety of living vertebrates and created a family tree that provides an indication of the ancestral genes.

An enzyme from the ancestor of all vertebrates. The colored parts are locations of uncertainty, where modern versions differ from each other. Gumulya et al./Nature Catalysis

The authors inserted their approximation of the ancestral vertebrate into E.coli bacteria, which conveniently are one of the few modern living organisms that do not have their own P450s to mess things up.

The modified E.coli produced an enzyme as powerful as modern counterparts at room temperatures, but stable at  temperatures up to 66ºC (150ºF).

This stability was surprising, as the oceans had cooled substantially by the time the first vertebrates appeared, but Gillum said; "probably indicates that the thermostability was gradually lost in the absence of a need to survive high temperatures".

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