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Flavonoids are plant-derived secondary metabolites that protect plants from pathogens, parasites and abiotic stress, such as extreme weather and temperatures — they essentially act as the plants’ immune system, said , former chair of biochemistry and molecular biology at Michigan State University. Grotewold also serves on the editorial board of the Journal of Biological Chemistry.

Erich Grotewold

“Let’s not forget that plants can’t move when their environments get uncomfortable,” Grotewold said, emphasizing the importance of plant specialized metabolic pathways and products.

Flavonoids are a component of the phenylpropanoid biosynthesis pathway. They were once colloquially known as “” for their antioxidant properties, and their production and sales contribute U.S. dollars every year to the global economy. While not all flavonoids are pigmented, these molecules produce pigments that give flowers their deep, rich colors.

“Flavonoids have contributed (to what) we understand as modern genetics today,” Grotewold said. Indeed, flavonoid studies from the 1980s led to the discovery of the “,” short segments of DNA that can move from one genomic location to another, and , which is now a common tool in research and biotechnology.

Grotewold was this month’s speaker on ASBMB Breakthroughs, a webinar series highlighting research from ɬÀï·¬ journals. During his talk, sponsored by JBC, he shared his discovery that flavonoid gene regulation is controlled by the interaction between transcription factors, rather than their DNA-binding specificity.

“My journey into plants started by trying to figure out how (the two branches of the flavonoid biosynthesis pathway), which involve the same DNA-binding domain and in some regards, very similar compounds, are differentially regulated,” said Grotewold.

Some flavonoids produce pigments that give flowers and fruits their colors.

In corn, the flavonoid biosynthesis pathway forks into two branches: one forms phlobaphenes, a pigment that is unique to grass plants, and the other, anthocyanins, which are more widely distributed throughout the plant kingdom. These branches are regulated by the transcription factors P1 and C1, respectively. However, Grotewold explained, both P1 and C1 contain the same DNA-binding domain, known as MYB, and thus have very similar DNA-binding specificities.

Genes in the anthocyanin biosynthesis pathway are regulated by the physical interaction between the MYB domain on C1 and another transcription factor called R. Grotewold that six amino acids on C1, four of which are on the solvent-exposed surface of MYB, confer C1’s specificity for R. When Grotewold substituted the amino acids at these positions on P1 for those found on C1, the modified P1 protein gained the ability to interact with R and activate the anthocyanin pathway.

Grotewold and his colleagues that R can act as a “regulatory switch” — the configuration of one of R’s domains, called ACT, can determine whether it interacts with MYB, and subsequently, which genes are being targeted and which pathways activated. This indicated that gene regulation in flavonoid biosynthesis depends on the interaction between transcription factors, not DNA binding specificity, Grotewold said.

“We now know that this six amino acid motif that we initially found in C1 regulates a lot of different processes in plants, even beyond the formation of anthocyanin pigment (the pathway’s end-product in corn),” he added.

More recently, Grotewold’s team has been studying flavonoid biosynthesis in Arabidopsis thaliana, a small flowering plant in the mustard family. They found that naringenin chalcone, one of the pathway intermediates, can interact with and stabilize ultraviolet-B receptor protein, or UVR8, in a UV-independent manner. Grotewold said that he found this surprising not only because UV-independent functions of UVR8 were previously unknown, but also because it suggested that naringenin chalcone may be more important than once expected.

“We typically ignore pathway intermediates because we think of them as biologically inactive,” Grotewold said, “But we saw that they can have very important regulatory activities.”

Up next

Ileana Cristea

TBD

June 18, 2025  12:15–1 p.m. Eastern
Ileana Cristea of Princeton University will present her research on using mass spectrometry to study viruses.