Uricase: the enzyme humans lost

Nearly every living thing, from bacteria to dogs, carries an enzyme that breaks down uric acid. Humans and the great apes do not. The story of that enzyme, urate oxidase, is a good way into both evolution and the business of finding useful enzymes in microbes.

What urate oxidase does

Wikipedia's article on urate oxidase, also known as uricase, describes it as a metabolic enzyme found in nearly all species from bacteria to mammals. It catalyses the oxidation of uric acid, the first step in a short series of reactions that ends with a substance called allantoin. In organisms that have the enzyme, uric acid is therefore an intermediate, passed along and converted, rather than an end point.

Uric acid itself comes from the breakdown of purines, the building blocks found in DNA and RNA and in several important cellular molecules. Every cell turns over these molecules, so every organism has to deal with the products. Where urate oxidase is present, the pathway continues past uric acid; where it is absent, it stops there.

The enzyme humans lost

The Wikipedia article explains that in humans, great apes and certain New World monkeys, the gene for urate oxidase exists only as a pseudogene, a broken copy that no longer makes a working enzyme, having been lost during primate evolution. As a result, the pathway in these primates ends with uric acid instead of allantoin, and the article notes that humans and many primates have much higher and more variable levels of urate in the blood than most other mammals.

Why the loss happened is a question for evolutionary biology rather than for this guide, but its consequence is simple to state: a whole branch of the primate family depends on other routes to handle uric acid that most animals would simply convert. That makes the enzyme a subject of interest in biochemistry and in medicine, and it means that the enzyme itself, when researchers want it, has to come from some other organism.

Many origins, one reaction

The enzyme has another curiosity. According to the same article, urate oxidase is a notable example of non-homologous isofunctional enzymes: proteins with independent evolutionary origins that catalyse the same chemical reaction. Besides the classic enzyme, found in all three domains of life, some bacteria carry unrelated proteins that do the same job using different helper molecules. Nature, in other words, has invented the solution more than once.

For enzyme hunters this is encouraging. It suggests that the diversity of microbial life holds several different tools for the same task, some of which may be better suited than others to a given use, whether that means tolerating heat, working at a particular acidity or being easier to produce.

Microbes as enzyme sources

Most enzymes used commercially come from microorganisms. Wikipedia's article on industrial enzymes describes how they are used across pharmaceuticals, chemical production, biofuels, food and consumer products, and explains that scaling up enzyme production requires optimising the fermentation process: most enzymes are produced under aerobic conditions and need a constant supply of oxygen, which shapes the design of the fermenter.

Finding a good producer usually starts with screening. A researcher collects samples from environments where the enzyme's substrate is plentiful, since organisms living there are likely to have ways of using it. Soil, compost, animal waste and industrial residues are all common hunting grounds. The samples are grown on media where the target substance is present, sometimes as the main food source, so that organisms able to use it stand out. Colonies that show activity are purified and tested further, and the best candidates are grown under different conditions to see how much enzyme they make and how stable it is.

This cycle of isolate, test, compare and optimise is the same whether the enzyme sought is an amylase for starch, a xylanase for plant fibre or an oxidase like uricase. The steps are routine; what varies is the ingenuity of the screen and the patience needed to follow up the few promising strains among many.

Reading enzyme studies

Papers that report a new enzyme-producing strain usually describe where it came from, how it was identified, the conditions under which it produced the most enzyme, and the enzyme's behaviour with temperature and acidity. Reading them well means noticing the scale of the work: a strain that performs well in a shaken flask has only started the journey toward any practical use, and a single strain from a single sample says little about how common the ability is.

It also means keeping the biology separate from any medical question. Uricase appears in medical research because of the primate loss described above, but this page is about the enzyme as biochemistry and as a product of microbes. Nothing here is medical advice.