Plants constantly adjust their metabolism to cope with changing environmental conditions. A key pathway involved in this process is the phenylpropanoid pathway which produces important compounds such as flavonoids, lignin, and salicylic acid, helping plants respond to stress and regulate growth. However, one fundamental question is unclear: how do plants prevent metabolic overload when flavonoids accumulate to high levels?

A study published in Science Advances and led by Prof. ZHAO Qiao from the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences uncovered a molecular "braking system" that helps plants keep the phenylpropanoid pathway in balance. Researchers revealed that he enzyme phenylalanine ammonia-lyase (PAL), which initiates this pathway, can move into the nucleus and act as a molecular brake on flavonoid production.

PAL has long been regarded as a cytoplasmic enzyme responsible for the first step of phenylpropanoid metabolism. Researchers discovered that PAL also accumulated in the nucleus. This nuclear localization was dynamic and reversible: when flavonoid biosynthesis was enhanced by ultraviolet (UV)-B irradiation or high sucrose treatment, PAL became enriched in the nucleus; once the stimulus was removed, it returned to the cytoplasm.

Researchers found that this process did not require new protein synthesis, suggesting that PAL participated in metabolic regulation through rapid and reversible changes in its subcellular location. Further analyses showed that phosphorylation acted as a key molecular switch controlling the nuclear translocation of PAL.

Furthermore, researchers discovered that nuclear PAL suppressed flavonoid biosynthesis through two coordinated mechanisms. First, its movement into the nucleus reduced the amount of active enzyme in the cytoplasm, lowering metabolic flux. Second, nuclear PAL interfered with a transcription complex that activated flavonoid biosynthetic genes, reducing gene expression. These effects created a feedback loop: when flavonoid metabolites accumulated, PAL moved into the nucleus and slowed flavonoid production.

This study reveals a new role of PAL besides its classical function as a metabolic enzyme. It provides new insights into plant metabolic regulation and may offer new strategies for engineering plant metabolism and producing valuable natural compounds.