Structure and Total Synthesis of Lysobactin (Katanosin B)

Abstract

Tackle‐resistant bacteria: Determination of the 3D structure of the antibiotic lysobactin has led to its total synthesis and resulted in a high‐yielding macrolactamization step. The minimal use of protecting groups allowed preorganization of the side chains to steer the cyclization. Thus, a new chemical route has been developed in the search for innovative antibiotic lead structures.

The Mechanism of Action of Lysobactin

“…2 In 2007, two groups independently described the total synthesis of lysobactin, and in 2011 the gene cluster was identified and characterized. 11 To enable assessment of analogues for possible development, we further characterized lysobactin’s activity and determined its mechanism of action.…”

Lipid-II forms potential “landing terrain” for lantibiotics in simulated bacterial membrane

“…It's important to note that DMSO is very rough mimic of the membrane, so the actual structure of this complex in the membrane may be different. Several other lantibiotics and antimicrobial peptides, including mersacidin14, ramaplanin15, katanosin16, plectasin17 and others, bind to pyrophosphate as well, although interaction sites most probably differ from each other and typically embrace one or both sugar residues of peptidoglycan part. Although much effort has been spent for rationalization of structure–activity relationships of lantibiotics18, molecular aspects of their action are still unclear, especially when it comes to real bacterial membranes.…”

Multipler Angriff auf Bakterien durch das neue Antibiotikum Teixobactin

“…Negativ geladene Aminosäuren scheinen außer beim Plusbacin (kompensiert durch Ca 2+ -Bindung) vollkommen zu fehlen. Besonders auffällig an Te ixobactin ist die strukturelle Nähe zu Katanosin B(3), [8] sieht man von der bei Te ixobactin vergleichsweise kleinen Ringgrçße ab. [9] In ihrer Summenformel unterscheiden sich Te ixobactin und Katanosin Bn ur wenig (C 58 …”