Kinetic Growth of Multicomponent Microcompartment Shells

Abstract

An important goal of systems and synthetic biology is to produce high value chemical species in large quantities. Microcompartments, which are protein nanoshells encapsulating catalytic enzyme cargo, could potentially function as tunable nanobioreactors inside and outside cells to generate these high value species. Modifying the morphology of microcompartments through genetic engineering of shell proteins is one viable strategy to tune cofactor and metabolite access to encapsulated enzymes. However, this is a difficult task without understanding how changing interactions between the many different types of shell proteins and enzymes affect microcompartment assembly and shape. Here, we use multiscale molecular dynamics and experimental data to describe assembly pathways available to microcompartments composed of multiple types of shell proteins with varied interactions. As the average interaction between the enzyme cargo and the multiple types of shell proteins is weakened, the shell assembly pathway transitions from (i) nucleating on the enzyme cargo to (ii) nucleating in the bulk and then binding the cargo as it grows to (iii) an empty shell. Atomistic simulations and experiments using the 1,2-propanediol utilization microcompartment system demonstrate that shell protein interactions are highly varied and consistent with our multicomponent, coarse-grained model. Furthermore, our results suggest that intrinsic bending angles control the size of these microcompartments. Overall, our simulations and experiments provide guidance to control microcomparmtent size and assembly by modulating the interactions between shell proteins.

Modeling bacterial microcompartment architectures for enhanced cyanobacterial carbon fixation

“…This is further underpinned by the multitude of different shell proteins BMCs can encode and their synthetic interchangeability ( Cai et al., 2015b ; Slininger Lee et al., 2017 ) which certainly influence shell-shell (including curvature) and shell-cargo/scaffold interactions. For example, many BMCs encode for BMC-T proteins where every other edge may be better attuned for specific shell interactions on adjacent subunits ( Trettel et al., 2022 ; Waltmann et al., 2023 ) and influence factors like shell curvature and/or shell-cargo interactions. Many others bioinformatically identified BMC loci entirely lack these factors for unknown reasons ( Sutter et al., 2021 ).…”