Quantitative Single-Cell Mass Spectrometry Provides a Highly Resolved Analysis of Natural Product Biosynthesis Partitioning in Plants

Plants produce an extraordinary array of natural products
(specialized
metabolites). Notably, these structurally complex molecules are not
evenly distributed throughout plant tissues but are instead synthesized
and stored in specific cell types. Elucidating both the biosynthesis
and function of natural products would be greatly facilitated by tracking
the location of these metabolites at the cell-level resolution. However,
detection, identification, and quantification of metabolites in single
cells, particularly from plants, have remained challenging. Here,
we show that we can definitively identify and quantify the concentrations
of 16 molecules from four classes of natural products in individual
cells of leaf, root, and petal of the medicinal plant Catharanthus roseus using a plate-based single-cell
mass spectrometry method. We show that identical natural products
show substantially different patterns of cell-type localization in
different tissues. Moreover, we show that natural products are often
found in a wide range of concentrations across a population of cells,
with some natural products at concentrations of over 100 mM per cell.
This single-cell mass spectrometry method provides a highly resolved
picture of plant natural product biosynthesis partitioning at a cell-specific
resolution.