The missing piece of the RuBP puzzle is of course the other carboxysome shell components not featured in this study. The minimal model we simulate here (Fig. ) contains two types of shell proteins, whereas all carboxysomes containing organisms 384 encode at least one trimeric shell protein with hexagonal 385 symmetry. Comparing available cryo-EM structures for the 386 BMC-trimer and hexamer shell proteins , the 387 stacked trimer sub-unit has a larger, gated pore that may 388 facilitate RuBP transport. Future study will be required to 389 assess the relative permeability between the two components, 390 as the trimer is typically far less abundant on the carboxysome 391 surface compared to the hexamer proteins. 392 pH effects on the CCM. A compelling hypothesis in the wider 393 carboxysome literature is that there is a pH gradient across 394 the carboxysome shell , and that pH plays a role in car-395 boxysome regulation, with lower intracarboxysomal pHs asso-396 ciated with higher metabolic activity . Lower pH supports 397 robust carbonic anhydrase activity, which combines free pro-398 tons (H + ) from solution with bicarbonate (HCO3 -) to form 399 CO2 and H2O. While it remains elusive and challenging to 400 determine the role of pH in a carboxysome, systems biology 401 predictions with a pH aware model shed light on the 402 optimal interior pH for carboxysome function relative to the 403 cyanobacterial cytosol pH (∼ 8) . In contrast to ear-404 lier models, where the optimal carboxysome permeability was 405 between 10 -2 -10 -3 cm/s , the pH aware model has the 406 optimal carboxysome permeability at 10 -4 cm/s (20), how-407 ever the revised model does support carbon fixation for CO2 408 permeability of 10 -2 cm/s. Next, comparing RuBP transport 409 across the synthetic shell, from MD simulations we derive 410 the permeability to be 4.4 × 10 -4 cm/s (Table ), which is 411 similar to the optimal range reported by Long et al for a 412 carboxysome of radius 50 nm and compartment pH between 7 413 -8.