Ecologically Informed Design of Synthetic Microbial Community Enables Robust Degradation and Engraftment for Antibiotic Removal in Wastewater

Conventional biological wastewater treatment often fails
to remove
emerging contaminants (ECs) because specialized degraders are absent.
We developed a function-ecology-integrated framework for designing
synthetic microbial communities (SynComs) by combining metagenome-guided
identification of degradation potential, quorum-sensing functionality
screening, and keystone-based selection from genome-scale metabolic
models (GSMMs). Applied to sulfamethoxazole (SMX) degradation, this
approach identified five strains with stable catabolic potential and
high ecological coherence. GSMM simulations predicted SynCom5 (three
species) and SynCom11 (four species) would achieve the highest SMX
uptake fluxes (30.7 and 31.7 mmol gDW–1 h–1, respectively), driven by complementary amino acid cross-feeding
and a high ratio of metabolic interaction potential to resource overlap.
Experimentally, both SynComs removed >90% of SMX within 72 h, with
SynCom11 selected for bioaugmentation. In activated sludge microcosms,
SynCom11 achieved 91.3% SMX removal over 7 days, compared to 25.8%
in controls, and successfully engrafted 2 of its 4 members. This approach
avoids high-concentration selective pressure, minimizing resistance
risks, and demonstrates that embedding an ecologically informed design
within catabolic function enables robust, scalable bioaugmentation
for ECs.