Impact of a Stereocentre Inversion in Cyclic Lipodepsipeptides from the Viscosin Group: A Comparative Study of the Viscosinamide and Pseudodesmin Conformation and Self‐Assembly

The viscosin group covers a series of cyclic lipodepsipeptides (CLPs) produced by Pseudomonas bacteria, with a range of biological functions and antimicrobial activities. Their oligopeptide moieties are composed of both L ‐ and D ‐amino acids. Remarkably, the Leu5 amino acid—centrally located in the nonapeptide sequence—is the sole residue found to possess either an L or D configuration, depending on the producing strain. The impact of this D / L switch on the solution conformation was investigated by NMR‐restrained molecular modelling of the epimers pseudodesmin A and viscosinamide A. Although the backbone fold remained unaffected, the D / L switch adjusted the segregation between hydrophobic and hydrophilic residues, and thus the amphipathicity. It also influenced the self‐assembly capacity in organic solvents. Additionally, several new minor variants of viscosinamide A from Pseudomonas fluorescens DR54 were identified, and an NMR assay is proposed to assess the presence of either an L ‐ or D ‐Leu5.