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SummaryProtists in the gut microbiota influence intestinal immunity and epithelial composition, yet the mechanisms used by these protists to shape the gut environment remain poorly understood. Here, we identify a new protist species, Tritrichomonas casperi, and show that metabolic differences between closely related commensal protists modulate their effects on host immunity and determine their ecological niche within the murine microbiota. Genomic and metabolomic analysis of commensal tritrichomonads reveal species-level differences in excretion of the tuft cell activating metabolite succinate, leading to differential induction of Th1, Th2, and Th17 cells in the small intestine. Using defined diets and in vitro growth assays, we show that different tritrichomonad species preferentially rely on dietary polysaccharides or mucus glycans, which leads to trans-kingdom competition with specific bacteria in the microbiota. Our findings elucidate differences in commensal tritrichomonad metabolism and suggest how dietary interventions could regulate the impact of these protists on gut health.

Synthetic materials are integral components of consumable and durable goods and are indispensable in the modern world. Polyesters are the most versatile bulk- and specialty-polymers but their production is not sustainable and their fate at end-of-life is of great concern. Bioplastics are highly regarded alternatives but often fall behind conventional synthetic plastics due to shortcomings in material properties and commercial competitiveness. This has limited the success of sustainable replacements at global market scale. Enabling production of bioplastics with superior properties from waste-derived feedstocks could change that. To this end, we created a synthetic entry into the metabolic pathway of bio-polyester synthesis ofCupriavidus necatorH16 by means of heterologous hydroxyacyl-CoA transferase and mutant PHA synthase. The resulting microbial cell factories produced a range of aliphatic and aromatic biopolyesters and enabled co-polymerization of a range of hydroxy carboxylates, including a hydroxyphenylic and a hydroxyfuranoic acid, for the first time incorporating aromatic rings in the backbone of biological polyesters. These diverse polymers were then characterized in terms of their physical properties. The resulting polymers were structurally analogous to synthetic polyesters like PET, PEF and other polyarylates. In a further advance, the transgenic strain was cultivated in a bio-electrochemical system under autotrophic conditions, enabling synthesis of aromatic bio-polyesters fromin-situgenerated O2, while assimilating CO2. Follow-up elementary flux-mode analysis established the feasibility ofde novoproduction of twenty different polyesters from five different carbon- and energy-sources. This comprehensive study opens the door to sustainable bio-production of various high-performance thermoplastics and thermosets.Significance statementBiomaterials can facilitate the transition of chemical industry to a carbon-neutral and circular economy and prevent the accumulation of greenhouse gases and plastic waste in the natural environment by developing bio-replacements for existing fossil carbon-based plastics along with end-of-life strategies. Accomplished via the genetic engineering of a microbial cell factory that assimilates carbon dioxide, this work demonstrates the first biocatalytic polymerization of aromatic building blocks and their incorporation into the backbone of a bio-polyester. Employing a bio-electrochemical system for cultivation of the microbes, oxyhydrogen is formed and consumedin-situ, thus avoiding explosive gasmixtures. The obtained aromatic polyesters are structural analogs to synthetic bulk- and high-performance polymers such as PET (polyethylene terephthalate) and PEF (polyethylene furanoate).Highlights-First demonstration of bio-polyarylates – microbial polyesters with aromatic rings in the backbone-Production of novel PHAs from CO2and H2+O2achievedin-situin a bio-electrochemical system-Expression-level of PHA synthase and molecular weight of polyesters is inversely correlated-In silicodesign and pathway analysis of bio-polyesters from low-cost carbon-feedstocks