SCIENTISTS DISCOVER KEY LINK TO REGULATORS OF PLANT GROWTH AND DEVELOPMENT

Researchers suspect new clues to plant biosynthesis may reveal insights into physiology of mammals

San Diego, Calif. (January 11, 2001)-- Leading non-profit research institutes Human BioMolecular Research Institute (HBRI) (www.HBRI.org) and The Salk Institute (www.salk.edu) announced today that a study they conducted jointly has been reported in the January 12th issue of Science. Findings link a plant enzyme, flavin-containing monooxygenase, to the biosynthesis of a powerful growth hormone, elucidating important clues to the mechanism of plant hormone biosynthesis, which may eventually lead to physiological insights about mammalian biochemistry as well, according to John Cashman, Ph.D., HBRI Director.

Investigators have discovered a key link between the metabolism of tryptamine by the flavin-containing monooxygenase and metabolites serving as powerful regulators of plant growth and development, including cell division and elongation, differentiation, tropisms and flowering. Research finding were reported by investigators Yunde Zhao, Ph.D., Joanne Chory, Ph.D., and their colleagues from the Salk Institute, John Cashman, Ph.D., of Human BioMolecular Research Institute and Jerry Cohen, Ph.D., from the University of Minnesota. More specifically, according to the report, results have tied a specific metabolic enzyme, called the flavin-containing monooxygenase (FMO), to the production of tryptamine hydroxylamine and indole-3-acetaldoxime, two intermediates in auxin (or plant growth hormone) synthesis in Arabidopsis.

Auxin is an essential plant hormone that influences many aspects of plant growth and development, including cell division and elongation, differentiation, tropisms, apical dominance, senescence and flowering. Although auxins have been studied for more than 100 years, the mechanisms of the hormone's biosynthesis and action remain elusive.

According to lead investigator Zhao, when the gene-encoding FMO was introduced into the plant and expressed at an elevated level, it lead to overproduction of auxin in Arabidopsis. Elevated levels of auxin were responsible for the observed phenotype that included increased root hair growth and decreased apical hook formation.

The gene in plants responsible for auxin formation is similar to the FMO gene in mammals and contains conserved motifs for FAD and NADPH binding, the scientists reported. The study's detailed analysis of the Arabidopsis genome indicated that there are at least 11 homologous genes. These genes may express proteins with overlapping or redundant function, which may explain why auxin-deficient mutants have not been previously observed according to Zhao.

"The finding that there are several genes involved in overlapping functions may help us to understand some of the more mysterious responses of plants to different stimuli and stages of development," according to David P. Ballou, Ph.D., Professor of Biological Chemistry at the University of Michigan’s Department of Biological Chemistry "This work should have broad impacts to the understanding of the chemical events involved in signal transduction of growth and development. Thus, biotechnology will reap large benefits in their goals of engineering more productive plants," he said. "In addition, because similar FMOs are found in mammals, some of the principles of regulation learned here may be relevant to human growth and development."

The San Diego and Minnesota team, expanding previous studies suggesting that metabolism of tryptophan was a component of the auxin biosynthetic pathway, investigated the role of FMO in auxin biosynthesis. The researchers first found that the gene encoding FMO in plants forms the hydroxylamine of tryptamine and that this is the rate-limiting step in auxin biosynthesis in many plants.

The study, funded in part by the National Institute of General Medical Sciences of the National Institutes of Health and the Howard Hughes Medical Foundation, also revealed that elevated levels of the gene leads to overproduction of auxin in Arabidopsis and that elevated auxin level is responsible for the observed phenotype.

Although mammalian FMO’s have been studied by biochemical means for more than 35 years, their physiological significance remains unknown. Further genetic and biochemical analysis of Arabidopsis FMOs may yield important clues to understanding the physiological role of their mammalian counterparts, according to John Cashman, Ph.D.

"The study by Zhao et al. is a major breakthrough in plant biology. The plant hormone indole-3-acetic acid (IAA or auxin) has a fundamental role in many aspects of plant growth and development," according to Mark Estelle, Ph.D., the D.J.Sibley Professor of Molecular Genetics at the Institute for Cellular and Molecular Biology, The University of Texas at Austin. "The work is sure to stimulate a flurry of new studies, investigating other members of the YUCCA family as well as upstream and downstream activities. It is also interesting to note that this work will lead to new hypotheses concerning the function of related enzymes in mammals."

About HBRI: The Human BioMolecular Research Institute is a non-profit research institute conducting basic research focused on unlocking biological and chemical principles related to diseases of the human brain. The institute conducts fundamental studies of central nervous system disorders and translates findings into new drug development to address human illness. In addition, the institute promotes scientific learning through community service and public access by disseminating information and sharing research with collaborators, colleagues and the public.

About The Salk Institute: The Salk Institute is a non-profit research institute conducting basic science research dedicated to the improvement of human health. The Salk Institute's two major areas of focus are molecular biology and genetics, and the neurosciences. Among the many human diseases whose origins Salk Institute scientists are striving to discover are cancer, AIDS, Alzheimer’s and birth defects. In addition, studies in plant biology are aimed at improving the quantity and quality of the world's food supply.