Cellular Crowding Improves Efficiency In Protein Factories

Modular enzymes called nonribosomal peptide synthetases manufacture many antibiotics and immune suppressants in the biomolecule-packed environment of cells. But the same syntheses under less crowded conditions outside the cell are inefficient, limiting potential biotechnology applications.

Zhihong Guo and colleagues at Hong Kong University of Science & Technology have attempted to work around this problem by mimicking the cell's crowded conditions in solution (Org. Lett., DOI: 10.1021/ol7030153). The researchers show that simulated crowding using an inert sucrose polymer prevents an enzyme from releasing premature intermediates during the synthesis of enterobactin, a cyclic peptide that microbes use to acquire iron.

Adding the polymer decreased dead end side products to negligible levels, although it didn't lead to an appreciable increase in enterobactin yield. It isn't clear how crowding suppresses the side products, but Guo's team plans to examine possible crowding-induced structural changes in the enzyme. Prior research by another group has already shown that nonionic detergents improve the efficiency of a related enzyme, most likely by interacting with peptide substrates.