Semisynthesis of a Bacterium with Non-canonical Cell-Wall Cross-Links

• Published in: Journal of the American Chemical Society Vol. 142; no. 25; pp. 10910 - 10913
• Main Authors: Dik, David A, Zhang, Nan, Chen, Jason S, Webb, Bill, Schultz, Peter G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 24.06.2020
• Subjects: Cell Engineering - methods; Cell Wall - metabolism; Escherichia coli - metabolism; Peptidoglycan - chemistry; Peptidoglycan - metabolism; Phenylalanine - analogs & derivatives; Phenylalanine - metabolism; Phenylalanine - toxicity; Sulfones - chemistry; Sulfones - metabolism; Sulfones - toxicity
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.0c02956

The cell wall is an elaborate framework of peptidoglycan that serves to protect the bacterium against osmotic challenge. This exoskeleton is composed of repeating saccharides covalently cross-linked by peptide stems. The general structure of the cell wall is widely conserved across diverse Gram-negative bacteria. To begin to explore the biological consequence of introducing non-canonical cross-links into the cell wall of Escherichia coli, we generated a bacterium where up to 31% of the cell-wall cross-links are formed by a non-enzymatic reaction between a sulfonyl fluoride and an amino group. Bacteria with these non-canonical cell-wall cross-links achieve a high optical density in culture, divide and elongate successfully, and display no loss of outer membrane integrity. This work represents a first step in the design of bacteria with non-canonical “synthetic” cell walls.