posted on 2023-01-31, 00:44authored bySaad Raza, Mykayla Miller, Björn Hamberger, Josh V. Vermaas
Plants synthesize small molecule diterpenes composed
of 20 carbons
from precursor isopentenyl diphosphate and dimethylallyl disphosphate,
manufacturing diverse compounds used for defense, signaling, and other
functions. Industrially, diterpenes are used as natural aromas and
flavoring, as pharmaceuticals, and as natural insecticides or repellents.
Despite diterpene ubiquity in plant systems, it remains unknown how
plants control diterpene localization and transport. For many other
small molecules, plant cells maintain transport proteins that control
compound compartmentalization. However, for most diterpene compounds,
specific transport proteins have not been identified, and so it has
been hypothesized that diterpenes may cross biological membranes passively.
Through molecular simulation, we study membrane transport for three
complex diterpenes from among the many made by members of the Lamiaceae family to determine their permeability coefficient
across plasma membrane models. To facilitate accurate simulation,
the intermolecular interactions for leubethanol, abietic acid, and
sclareol were parametrized through the standard CHARMM methodology
for incorporation into molecular simulations. To evaluate the effect
of membrane composition on permeability, we simulate the three diterpenes
in two membrane models derived from sorghum and yeast lipidomics data.
We track permeation events within our unbiased simulations, and compare
implied permeation coefficients with those calculated from Replica
Exchange Umbrella Sampling calculations using the inhomogeneous solubility
diffusion model. The diterpenes are observed to permeate freely through
these membranes, indicating that a transport protein may not be needed
to export these small molecules from plant cells. Moreover, the permeability
is observed to be greater for plant-like membrane compositions when
compared against animal-like membrane models. Increased permeability
for diterpene molecules in plant membranes suggest that plants have
tailored their membranes to facilitate low-energy transport processes
for signaling molecules.