Description:
<jats:title>Abstract</jats:title><jats:p>A new cyclic hexapeptide, baceridin (<jats:bold>1</jats:bold>), was isolated from the culture medium of a plant‐associated <jats:italic>Bacillus</jats:italic> strain. The structure of <jats:bold>1</jats:bold> was elucidated by HR‐HPLC‐MS and 1D and 2D NMR experiments and confirmed by ESI MS/MS sequence analysis of the corresponding linear hexapeptide <jats:bold>2</jats:bold>. The absolute configurations of the amino acid residues were determined after derivatization by GC‐MS and Marfey's method. The cyclopeptide <jats:bold>1</jats:bold> consists partially of nonribosomal‐derived <jats:sc>D</jats:sc>‐ and allo‐<jats:sc>D</jats:sc>‐configured amino acids. The order of the <jats:sc>D</jats:sc>‐ and <jats:sc>L</jats:sc>‐leucine residues within the sequence cyclo(‐<jats:sc>L</jats:sc>‐Trp‐<jats:sc>D</jats:sc>‐Ala‐<jats:sc>D</jats:sc>‐allo‐Ile‐<jats:sc>L</jats:sc>‐Val‐<jats:sc>D</jats:sc>‐Leu‐<jats:sc>L</jats:sc>‐Leu‐) was assigned by total synthesis of the two possible stereoisomers. Baceridin (<jats:bold>1</jats:bold>) was tested for antimicrobial and cytotoxic activity and displayed moderate cytotoxicity (1–2 μg mL<jats:sup>−1</jats:sup>) as well as weak activity against <jats:italic>Staphylococcus aureus</jats:italic>. However, it was identified to be a proteasome inhibitor that inhibits cell cycle progression and induces apoptosis in tumor cells by a p53‐independent pathway.</jats:p>