Novel approach for carbon-wise utilization of lignin-related compounds by synergistically employing anaerobic and aerobic bacteria

Lignin is a highly abundant but strongly underutilized natural resource that could serve as a sustainable feedstock to produce chemicals by microbial cell factories. However, the production from lignin-related aromatics is hindered by limited substrate range and inefficient catabolism of the production hosts. Particularly, the aerobic demethylation reactions are energy-limited and cause growth inhibition and loss of CO2. Here, we present a novel approach for carbon-wise utilization of lignin-related aromatics by the integration of anaerobic and aerobic metabolisms. In practice, we employed an acetogenic bacterium Acetobacterium woodii for anaerobic O-demethylation of aromatic compounds, which distinctively differs from the aerobic demethylation; in the process, the carbon from the methoxyl groups is fixated together with CO2 to form acetate while the aromatic ring remains unchanged. These accessible end-metabolites were then utilized by an aerobic bacterium Acinetobacter baylyi ADP1. Finally, we demonstrated the production of muconic acid from guaiacol, an abundant but inaccessible substrate to most microbes, with a nearly equimolar yield with only a minor genetic engineering and without the need for additional organic carbon source. This study highlights the power of synergistic integration of distinctive metabolic features of bacteria, thus unlocking new opportunities for harnessing microbial cocultures in upgrading challenging feedstocks.