Chemist finds enzymes that ‘just say no to acid’

A University chemist has found surprisingly tough enzymes in a bacterium that “just say no to acid.”

Acid resistance is a valued trait for both pills and human pathogens. The bacterium Acetobacter aceti makes unusually acid-resistant enzymes in spades, which could make the organism a source for new enzyme products and new directions in protein chemistry.

A. aceti has been used for millenniums to make vinegar, at least since an indirect reference in the Old Testament Book of Numbers to “vinegar made from wine.” But not until recently did anyone study the unusual biochemical features of the organism that allow it to survive — and even thrive — in very acidic conditions.


T. Joseph Kappock, Ph.D., assistant professor of chemistry in Arts & Sciences, couldn’t overlook this very promising bacterium.

“The thing that piqued our interest was that this organism has this weird growth habit of making vinegar from ethanol (alcohol), which means it’s highly resistant to ethanol, which very few things grow in, and resistant to acetic acid (vinegar), which even fewer things grow in,” Kappock said.

“Important enzymes in this bug resist acid in a way almost all organisms cannot, and we’re trying to answer the question, ‘How is this enzyme different?'”

That answer, Kappock said, could reveal many important insights.

Kappock discussed his research at the American Chemical Society’s annual meeting held recently in Philadelphia.

Specifically, Kappock and his research group study the enzyme citrate synthase, one of the oldest enzymes in a cell. Citrate synthase is important because it initiates the citric acid cycle, or Krebs cycle, a biochemical pathway vitally important for energy production in the cells of organisms as simple as bacteria and as complex as humans.

There also are a couple of ways Acetobacter could produce industrially applicable information.

“There are people who want to make more stable proteins,” Kappock said.

“There are increasing numbers of industrial processes that use enzymes, which are the ultimate green catalyst. The more things we can do with enzymes, the better for the environment, because they have no waste products.”

Enzymes already are used in products as diverse as laundry detergents and various medications.

According to Kappock, the more long-range goal is to involve insights from studies of this bacterium with the numerous diseases caused by protein misfolding. Alzheimer’s disease, Lou Gehrig’s disease and possibly even cataracts begin with misfolded proteins.

“A lot of times, a mild acid-mediated unfolding of an enzyme precipitates these kinds of disease,” Kappock said. “Insights from these marvelous Acetobacter enzymes might lead to making more stable enzymes or elucidating ways to treat these debilitating diseases.

“There are a lot of things that this research could help, but it’s at a basic stage now.”

Still, the research is promising enough to have been awarded federal and private funding.

Kappock is a little surprised that relatively few others have studied Acetobacter, given the common and widespread nature of the organism.

“It’s literally garden-variety,” he said. “Acetobacter clings to plant surfaces in the wild. For example, a big part of winemaking is excluding the grape skins from the wine because the bug lives there.”

Plants, microorganisms and their proteins are the bases for developing valuable drugs.

“Many antibiotics are derived from soil organisms like bacteria that are trying to kill other bacteria,” Kappock said.

Fortunately, in the case of Acetobacter, any useful enzymes it may provide should be completely harmless, just as it is to humans (besides ruining their wine).

“I think it’s likely going to be a piece of a larger story,” Kappock said. “What I’m hoping to get out of it is a better understanding of how proteins work. Our contribution is to find out how a couple of examples work and seeing if we can find general principles.”