(582ak) Encapsulation of Heterologous Pathways Within the Pdu Microcompartment of Salmonella Enterica

Bacterial
microcompartments are subcellular protein structures that encapsulate certain
pathways in bacterial cells. They provide some of the same function as the
organelles of eukaryotes.  A microcompartment is made up of many hexameric and
pentameric shell proteins that fit together to form a polyhedral shape about
100 nm across.  These protein shells may be used to enhance kinetics and
product yield of a series of enzymatic reactions by imparting several
advantages: increased proximity of enzymes, isolation of toxic intermediates,
insulation from inhibitors in the cytosol, and concentration of substrates.
These effects have been exhibited by native microcompartments such as the
carboxysome in chemoautotrophs and the propanediol utilization (Pdu) microcompartment
in Salmonella. It is of interest to learn whether these benefits are
also observed for heterologous pathways localized to the microcompartment. To
that end, three pathways were expressed in Salmonella and localized to
the Pdu microcompartment. Each was chosen to examine a putitative benefit of
encapsulation. Here, we discuss the functionality of each encapsulated pathway as
compared to the same pathway in the cytosol.  Moreover,
we present a strategy for optimizing the Pdu shell proteins for compatibility
with non-native metabolites, a potentially critical barrier to successful
heterologous pathway encapsulation.