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Microbial communities have vital roles in systems essential to human health and agriculture, such as gut and soil microbiomes, and there is growing interest in engineering designer consortia for applications in biotechnology (e.g., personalized probiotics, bioproduction of high-value products, biosensing). The capacity to monitor and model metabolite exchange in dynamic microbial consortia can provide foundational information important to understand the community level behaviors that emerge, a requirement for building novel consortia. Where experimental approaches for monitoring metabolic exchange are technologically challenging, computational tools can enable greater access to the fate of both chemicals and microbes within a consortium. In this study, we developed an in-silico model of a synthetic microbial consortia of sucrose-secreting Synechococcus elongatus PCC 7942 and Escherichia coli W. Our model was built on the NUFEB framework for Individual-based Modeling (IbM) and optimized for biological accuracy using experimental data. We showed that the relative level of sucrose secretion regulates not only the steady-state support for heterotrophic biomass, but also the temporal dynamics of consortia growth. In order to determine the importance of spatial organization within the consortium, we fit a regression model to spatial data and used it to accurately predict colony fitness. We found that some of the critical parameters for fitness prediction were inter-colony distance, initial biomass, induction level, and distance from the center of the simulation volume. We anticipate that the synergy between experimental and computational approaches will improve our ability to design consortia with novel function. Author summary: Microbial communities, play important, yet poorly understood roles in health and agriculture. As we develop a better understanding of how these communities interact together, as well as with their host organisms, there is growing interest in engineering communities with specific functions, such as for treating disease, personalized probiotics, or aiding plants with nutrient uptake. To better understand how these microbes interact with each other, we want to monitor the exchange of metabolites and the locations of the microbes, tasks which at present are technically challenging, if not impossible. Where experimental approaches for monitoring metabolites are limited, computational tools can enable greater access to the fate of both chemicals and microbes within a community. In this study, we developed a computerized model of a synthetic microbial community of two bacteria, one which performs photosynthesis and supplies sugar and another which consumes the sugar for growth. We showed that the relative level of sugar secretion regulates not only the steady-state support for the consumer partner's growth, but also how the community changes with time. To determine the importance of spatial organization within the community, we fit a model and used it to predict colony growth. We anticipate that the synergy between experimental and computational approaches will improve our ability to design microbial communities with new functions. [ABSTRACT FROM AUTHOR]

Bacterial microcompartments (BMC) are complex macromolecular assemblies that participate in varied chemical processes in about one fourth of bacterial species. BMC-encapsulated enzymatic activities are segregated from other cell contents by means of semipermeable shells, justifying why BMC are viewed as prototype nano-reactors for biotechnological applications. Herein, we undertook a comparative study of bending propensities of BMC hexamers (BMC-H), the most abundant shell constituents. Published data show that some BMC-H, like β-carboxysomal CcmK, tend to assemble flat whereas other BMC-H often build curved objects. Inspection of available crystal structures presenting BMC-H in tiled arrangements permitted us to identify two major assembly modes with a striking connection with experimental trends. All-atom molecular dynamics (MD) supported that BMC-H bending is triggered robustly only from the arrangement adopted in crystals by BMC-H that experimentally form curved objects, leading to very similar arrangements to those found in structures of recomposed BMC shells. Simulations on triplets of planar-behaving hexamers, which were previously reconfigured to comply with such organization, confirmed that bending propensity is mostly defined by the precise lateral positioning of hexamers, rather than by BMC-H identity. Finally, an interfacial lysine was pinpointed as the most decisive residue in controlling PduA spontaneous curvature. Globally, results presented herein should contribute to improve our understanding of the variable mechanisms of biogenesis characterized for BMC, and of possible strategies to regulate BMC size and shape. Author summary: Bacterial microcompartments are complex macromolecular ensembles that participate in varied metabolic processes in many microorganisms. They consist of a proteinaceous shell that encapsulates enzymatic cargo that mediate connected chemical reactions. Being confined within shells, the overall efficiency of the process is thought to augment, and reactions that imply toxic intermediates, which are lethal to the host in free-diffusing context, become feasible. These natural nano-reactors are therefore appealing for biotechnology purposes. Understanding how such complex objects form is essential. Experimental studies demonstrated the existence of two possible pathways. Thus, shell components grew onto a preformed core of organized cargo in cyanobacterial carboxysomes, whereas in Pdu compartments, both cargo and shell formation seemed to occur randomly. With the aim to contribute to the understanding of the different biogenesis pathways, here we investigated the trend of the most abundant protein constituents of bacterial micro-compartment shells to form curved structures. We first discovered the occurrence of two major assembly modes in deposited BMC-H crystal structures that clustered proteins in two groups that correlate well to their experimental propensities to form bent or flat structures. Subsequently, molecular dynamic simulations supported that only one of the modes is ready to curve. Moreover, simulations on protein mutants pinpointed a residue that seems to be pivotal in triggering bending. Globally, our data permit to draw a scenario that explains BMC biogenesis differences as a result of the capture of some BMC-H, such as CcmK of carboxysomes, in local minima corresponding to flat states that would delay closure of BMC shells, something that might require the intervention of other molecular effectors. [ABSTRACT FROM AUTHOR]