4-Phenylbutyric acid promotes plant regeneration as an auxin by being converted to phenylacetic acid via an IBR3-independent pathway

4-Phenylbutyric acid (4PBA) is utilized as a drug to treat urea cycle disorders and is also being studied as a potential anticancer drug that acts via its histone deacetylase (HDAC) inhibitor activity. During a search to find small molecules that affect plant regeneration in Arabidopsis, we found that 4PBA treatment promotes this process by mimicking the effect of exogenous auxin. Specifically, plant tissue culture experiments revealed that a medium containing 4PBA enhances callus formation and subsequent shoot regeneration. Analyses with auxin-responsive or cytokinin-responsive marker lines demonstrated that 4PBA specifically enhances AUXIN RESPONSE FACTOR (ARF)-dependent auxin responses. Our western blot analyses showed that 4PBA treatment does not enhance histone acetylation in Arabidopsis, in contrast to butyric acid and trichostatin A, other chemicals often used as HDAC inhibitors, suggesting this mechanism of action does not explain the observed effect of 4PBA on regeneration. Finally, mass spectroscopic analysis and genetic approaches uncovered that 4PBA in Arabidopsis plants is converted to phenylacetic acid (PAA), a known natural auxin, in a manner independent of peroxisomal IBR3-related beta-oxidation. This study demonstrates that 4PBA application promotes regeneration in explants via its auxin activity and has potential applications to not only plant tissue culture engineering but also research on the plant beta-oxidation pathway.

Automated summary

The drug 4-phenylbutyric acid (4PBA) has been found to promote plant regeneration in Arabidopsis by mimicking the effect of exogenous auxin. This study demonstrates that 4PBA enhances auxin responses by converting to phenylacetic acid (PAA) in plants, independent of its histone deacetylase (HDAC) inhibitor activity. This research is significant for plant tissue culture engineering and the study of plant beta-oxidation pathway.