Image copyright Getty Images Image caption Integrated decision: Cells take into account the full costs of building their "power plants"

Fast-growing bacteria, cancer cells, and even stem cells prefer to use fermentation to extract energy from sugar molecules, even in the presence of oxygen.

This has perplexed scientists for almost a century, because the alternative metabolic process for energy production - respiration - produces more energy from the same amount of sugar.

But scientists have now calculated that fermentation actually produces more energy per resource spent, once the cost of building the molecular machineries for each process is factored in.

The finding is published in the journal Nature and offers a fresh perspective for cancer research, the researchers believe.

Calculating the budget

Wine, cheese, and bread are just a few products of fermentation by microorganisms - a process they use to obtain energy from sugar molecules.

However, in the presence of oxygen, microorganisms have a choice between fermentation and respiration.

From the same amount of sugar, respiration yields more than twice the amount of energy that fermentation does.

Despite this, fast-growing cells prefer to use the less efficient fermentation process.

Needless to say, this puzzle has kept the scientific community in a bit of a… pickle since the 1920s when this phenomenon was first discovered (pickling is a food preservation technique that involves fermentation).

Whole system

To solve the puzzle, Prof Terry Hwa and his collaborators from UC San Diego took a step back and had a look at the whole cell as a system, rather than individual molecules or isolated pathways.

"We used the top-down strategy - understanding the connection between molecules at the bottom and the physiology at the top."

"For bacteria to grow fast, they need lots of ribosomes… and ribosomes making ribosomes", explained Terry as he emphasized that a lot of ribosomes are "tied up" in making the proteins for the fermentation and respiration machineries.

To get a handle on things, the researchers measured the resources involved in making each of these two machineries.

'Nuclear comparison'

The microorganism they used was Escherichia coli, the well-studied gut bacterium, and the technique was quantitative proteomics, allowing the identification and quantification of the proteins they were interested in.

When they drew the line and calculated the costs involved, Prof Hwa's team found that building and running the fermentation pathway was "cheaper" for fast growing cells.

This idea was first suggested several years ago by a group of theoretical biologists from the Netherlands, and Prof Hwa's team has provided the experimental evidence for it.

"What we discovered could be compared to the difference between generating energy by a coal factory versus a nuclear power plant," said Terry Hwa.

"Coal factories produce energy less efficiently than nuclear power plants on a per-carbon basis, but they are a lot cheaper to build."

A new perspective

"The cell is taking its growth into account. It's making an integrated decision."

Prof Hwa expressed hope that this work could be applied to cancer research.

"Cancer cells, and also stem cells, use fermentation to generate energy aerobically. We think our work brings a new perspective for cancer study."

The results may also have implications for biotechnology.

Prof Terry Hwa added: "Metabolic engineers are always trying to reduce metabolic waste in engineered organisms in order to reduce cost. Our findings suggest different strategies need to be devised to increase metabolic efficiency."