Symbiosis Is behind Rice Blight

Natural Products

Rice seedling blight, an economically costly agricultural disease, is caused by a toxin released by certain Rhizopus fungi. Long thought to be produced by the fungus itself, this toxin has now been shown to be biosynthesized by bacteria that live symbiotically inside the fungus.

This unexpected finding-by professor Christian Hertweck and graduate student Laila P. Partida-Martinez of the Leibniz Institute for Natural Products Research & Infection Biology in Jena, Germany-reveals a complex and unprecedented symbiotic alliance that pits fungus and bacterium against plant (Nature 2005, 437, 884). At the center of this alliance is rhizoxin, a macrocyclic polyketide natural product produced by the bacterium. Rhizoxin binding to a rice structural protein known as β-tubulin blocks cell division and weakens or kills the rice plant.

By showing that an antibiotic can be used to generate a symbiont-free fungus unable to produce rhizoxin, Hertweck and Partida-Martinez have revealed new strategies for controlling rice seedling blight. "It could be possible to control the disease by applying antibiotics rather than antifungal agents," Hertweck says.

Rhizoxin is a potent anticancer agent, but toxicity problems have prevented its use as a drug. Thanks to their success in cultivating the bacterium outside its fungal host, the researchers have been able to isolate rhizoxin, as well as novel rhizoxin analogs, Hertweck tells C&EN. His lab hopes that metabolic engineering may lead to other rhizoxin derivatives with improved properties.

"The exciting aspects of this research go beyond the prospects for controlling seedling blight in rice and using rhizoxin to treat cancer,"writes ecologist Ian R. Sanders of Switzerland's University of Lausanne in an accompanying Nature commentary. "The existence and evolution of such a symbiosis between the fungus and bacterium are in themselves intriguing."

What the partners get out of the alliance remains unclear. The fungus certainly profits from the nutrients provided by the decaying rice plant. But why doesn't the bacterium strike on its own? And how do both bacterium and fungus resist the toxic effects of rhizoxin? Hertweck's lab hopes that further study of this unusual alliance will provide answers to these questions.

Symbiotic natural product producers have recently been fingered in creatures as diverse as beetles, sponges, and microscopic marine animals. "The discovery of more and more examples of chemically mediated symbiotic complexity bodes well for drug discovery," comments medicinal chemist Eric W. Schmidt of the University of Utah. "These relationships may reveal new sources of novel natural products."