Even allocation of benefits stabilizes microbial community engaged in metabolic division of labor

Abstract

Metabolic division of labor (MDOL) is commonly observed in microbial communities, where a metabolic pathway is sequentially implemented by several members similar to an assembly line. Uncovering the assembly rules of the community engaged in MDOL is crucial for understanding its ecological contribution, as well as for engineering high-performance microbial communities. To investigate the assembly of the community engaged in MDOL, we combined mathematical modelling with experimentations using synthetic microbial consortia. We built a theoretical framework predict the assembly of MDOL system, and derived a simple rule: to maintain co-existence of the MDOL members, the populations responsible for former steps should hold a growth advantage (m) over the "private benefit" (n) of the population responsible for last step, and the steady-state frequency of the last population is determined by the quotient of n and m. Our experiments further indicated that our theoretical framework accurately predicted the stability and assembly of our engineered synthetic consortia that degrade naphthalene through two-step or multi-step MDOL. Our results demonstrate that the assembly of microbial community engaged in MDOL is determined by a limited number of parameters. This quantitative understanding provides novel insights on designing and managing stable microbial systems to address grand challenges facing human society in agriculture, degradation of the environment, and human health.

Genome-resolved analyses show an extensive diversification in key aerobic hydrocarbon-degrading enzymes across bacteria and archaea

“…Microorganisms are known to use division of labor or mutualistic interactions to perform HC degradation in the environment [57,58]. However, 92 genomes (less than 0.5%) of 23,446 investigated bacterial genomes do in fact, contain all the enzymes required to degrade at least one HC compound completely.…”

Guided by the principles of microbiome engineering: Accomplishments and perspectives for environmental use

“…Controlling the growth of different members could maintain their coexistence and stabilize the community [33][34][35] Engineered strains Cooperative interdependence Cooperative interdependence contributes to the maintenance of the long-term coexistence of multiple species [36] Natural strains Temperature Higher temperatures favor slower-growing bacterial species in multispecies communities…”

“…(2) Engineer a stable MDOL community with a defined structure [8,53] Model derived Metabolic burden; transfer efficiency An MDOL community outperforms a single population only when the benefit derived from reduced metabolic burden overcomes the inefficiency of intermediate transport [54] Engineered strains Parameters involved in a metabolic pathway To maintain the stability of an MDOL community, the populations responsible for the initial steps in a linear metabolic pathway should hold a growth advantage (m) over the "private benefit" (n) of the population responsible for the last step. The steady-state frequency of the last population is then determined by the quotient of n and m [33] Engineered strains Substrate concentration and toxicity The proportion of the population executing the first metabolic step in an MDOL community can be estimated by Monod-like formulas governed by substrate concentration and toxicity [55] synthetic consortia with predefined interaction modes to avoid such unpredictable effects. This type of design can be achieved by engineering the metabolism of the member strains or mimicking cell-cell communications through the construction of genetic circuits, usually based on quorumsensing signals.…”

“…54 Second, the members involved in an MDOL community cannot stably co-exist in some cases. In our recent study, we divided the degradation pathway of naphthalene into several steps and engineered several MDOL communities, in which each member was only able to perform one degradation step 33 . The MDOL communities are unstable because the strain performing the last step of the degradation pathway can obtain more benefits than other strains by privatizing available carbon sources.…”

“…This system can be simplified by imposing reasonable assumptions. For example, principles governing the function 54 and assembly 33 of microbial communities engaged in MDOL can be derived from the simplified LVMM model. The genome-scale metabolic model (GSMM) is another useful model for predicting community properties.…”