Tissue-specific circadian regulation of patchouli alcohol and diurnal control of pogostone biosynthesis in Pogostemon cablin

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The circadian clock helps plants adapt to daily environmental cycles by integrating internal and external cues to regulate physiological and metabolic processes. However, its role in the biosynthesis of specialized bioactive compounds remains poorly understood. Pogostemon cablin (patchouli), a medicinal plant that uniquely produces compounds such as patchouli alcohol and pogostone, serves as a valuable model for investigating the circadian regulation of specialized metabolism. In this study, we characterized the core circadian oscillator in P. cablin and generated both diurnal and circadian transcriptomic profiles from leaf and stem tissues. Our results show that, compared with the stem clock, the leave clock appears to serve as a key center for small molecule metabolism. Notably, patchouli alcohol accumulates rhythmically in the leaves in a circadian manner, whereas pogostone shows a diurnal rhythm of enrichment in the stems, with minimal accumulation of each compound in the opposite tissue. The distinct peak-to-trough amplitudes, with more than a two-fold difference, underscore the importance of timing and tissue specificity in optimizing harvest for maximum metabolite yield. A large number of biosynthetic enzyme genes exhibit rhythmic expression, and the core clock gene PcLUX interacts with the patchouli alcohol synthase gene PcPTS . This work reveals a previously uncharacterized link between the circadian clock and tissue-specific specialized metabolism in P. cablin , providing a molecular foundation for rhythm-guided harvesting and circadian-informed metabolic engineering to enhance the yield and sustainable production of natural bioactive compounds. • Circadian clock regulates leaf-specific rhythmic accumulation of patchouli alcohol. • Light/dark cycles regulate stem-specific rhythmic accumulation of pogostone. • Core clock gene PcLUX interacts with PcPTS to regulate patchouli alcohol production. • Proposed novel harvesting strategy to enhance compound yield by more than two-fold.