Xanthomonins I-III: a new class of lasso peptides with a seven-residue macrolactam ring.
Lasso peptides belong to the class of ribosomally synthesized and post-translationally modified peptides. Their common distinguishing feature is an N-terminal macrolactam ring that is threaded by the C-terminal tail. This lasso fold is maintained through steric interactions. The isolation and characterization of xanthomonins I-III, the first lasso peptides featuring macrolactam rings consisting of only seven amino acids, is now presented. The crystal structure of xanthomonin I and the NMR structure of xanthomonin II were also determined. A total of 25 variants of xanthomonin II were generated to probe different aspects of the biosynthesis, stability, and fold maintenance. These mutational studies reveal the limits such a small ring imposes on the threading and show that every plug amino acid larger than serine is able to maintain a heat-stable lasso fold in the xanthomonin II scaffold.
Fachbereich Chemie, Fachgebiet Biochemie und LOEWE-Zentrum für Synthetische, Mikrobiologie, Philipps-Universität Marburg, Meerwein-Strasse 4, 35032 Marburg (Germany).
Julian D
JD
Hegemann
Marcel
M
Zimmermann
Shaozhou
S
Zhu
Holger
H
Steuber
Klaus
K
Harms
Xiulan
X
Xie
Mohamed A
MA
Marahiel
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D005810:Multigene Family; D016296:Mutagenesis; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D043862:Rotaxanes / Q000737:chemistry / Q000378:metabolism*; D014974:Xanthomonas / Q000235:genetics / Q000378:metabolism
D007769:Lactams; D010455:Peptides; D043862:Rotaxanes; C000593090:xanthomonin I; C000593091:xanthomonin II; C000593092:xanthomonin III
biosynthesis; lasso peptides; macrocycles; natural products; steric hindrance