Enhancing cross-organelle coordination to advance plant cytochrome P450 functionality in yeast.

Sustainable production of plant secondary metabolites remains a substantial challenge. Microbial cell factories offer a promising solution, yet reconstituting plant cytochrome P450s, key enzymes in these pathways, remains a major hurdle. In this study, we investigated a plant membrane protein, AtMSBP1, for its ability to broadly enhance P450 functionality in engineered yeast. Unlike in plants, interactions with cytochrome P450s are not essential for AtMSBP1's function in yeast. Specifically, AtMSBP1 orchestrates interorganelle communication, involving not only the endoplasmic reticulum but also mitochondria and vacuoles, supporting cytochrome P450s functionality in yeast. This study highlights the critical role of cross-organelle coordination in supporting cytochrome P450s functionality, emphasizing a shift from traditional ER-based approaches to engineering cross-organelle interactions and tailoring the cellular microenvironment to enhance plant cytochrome P450s functionality in yeast.