Sander, K. B. | bioRxiv Science

bioRxiv2022

Towards Environmental Control of Microbiomes

Microbial communities have consequential effects on health and the environment yet remain uncontrollable due to their complex dynamics. Ecological modeling offers a platform to overcome their nonlinear and interconnected nature but traditionally does not account for context-dependence. Here, we extend the generalized Lotka-Volterra (gLV) model to accommodate a varying environment by identifying how environmental changes alter species growth rates and interactions in a manner that predicts full community trajectories across environmental gradients. We identify key environment-varying interactions within a synthetic community derived from the Oryzae sativa rhizosphere, and demonstrate how variations in the environment change fixed point compositions and rates of convergence. With our model, we simulate how precise perturbations of the environment can offer improvements in an optimal control problem of driving a community to a target composition. We show that environmental perturbation can minimize the total species input (direct species perturbation) and greatly expand the set of initial states from which a desired target can be reached despite stochasticity. This work demonstrates that a formal perspective on environmental influence of community dynamics is valuable for not only understanding seasonal changes or anthropogenic manipulations, but is critical for improving control of the microbiome.

systems biology↗

bioRxiv2022

Eliminating Genes for a Two Component System Increases PHB Productivity in Cupriavidus basilensis 4G11 Under PHB Suppressing, Non-Stress Conditions

Species of bacteria from the genus Cupriavidus are known, in part, for their ability to produce high amounts of poly-hydroxybutyrate (PHB) making them attractive candidate bioplastic producers. The native production of PHB occurs during periods of metabolic stress, and the process regulating the initiation of PHB accumulation in these organisms is not fully understood. Screening an RB-TnSeq transposon library of Cupriavidus basilensis 4G11 allowed us to identify two genes of an apparent, uncharacterized two component system which, when omitted from the genome, are capable of increased PHB productivity in balanced, non-stress growth conditions. We observe average increases in PHB productivity of 56% and 41% relative to the wildtype parent strain, upon deleting each of two genes individually from the genome. The increased PHB phenotype disappears, however, in nitrogen-free unbalanced growth conditions suggesting the phenotype is specific to fast-growing, replete, non-stress growth. Bioproduction modeling suggests this phenotype could be due to a decreased reliance on metabolic stress induced by nitrogen limitation to initiate PHB production in the mutant strains. Such strains may allow for the use of single stage, continuous bioreactor systems, which are far simpler than PHB bioproduction schemes used previously. Bioproductivity modeling suggests that omitting this regulation in the cells may increase PHB productivity up to 24% relative to the wildtype organism when using single stage continuous systems. This work furthermore expands our understanding of the regulation of PHB accumulation in Cupriavidus, in particular the initiation of this process upon transition into unbalanced growth regimes.

genomics↗