Imker, Heidi J.; Krahn, Daniel; Clerc, Jérome; Kaiser, Markus; Walsh, Christopher:
N-Acylation during Glidobactin biosynthesis by the tridomain nonribosomal peptide synthetase module GlbF.
2010
In: Chemistry & Biology, Jg. 17 (2010), Heft 10, S. 1077 - 1083
Artikel/Aufsatz in Zeitschrift2010Biologie
Fakultät für Biologie
Titel:
N-Acylation during Glidobactin biosynthesis by the tridomain nonribosomal peptide synthetase module GlbF.
Autor(in):
Imker, Heidi J.; Krahn, DanielLSF; Clerc, Jérome; Kaiser, MarkusLSF; Walsh, Christopher
Erscheinungsjahr
2010
WWW URL
Erschienen in:
Titel:
Chemistry & Biology
in:
Jg. 17 (2010), Heft 10, S. 1077 - 1083

Abstract:

Glidobactins are hybrid NRPS-PKS natural products that function as irreversible proteasome inhibitors. A variety of medium chain 2(E),4(E)-diene fatty acids N-acylate the peptidolactam core and contribute significantly to the potency of proteasome inhibition. We have expressed the initiation NRPS module GlbF (C-A-T) in Escherichia coli and observe soluble active protein only on co-expression with the 8 kDa MbtH-like protein, GlbE. Following adenylation and installation of Thr as a T-domain thioester, the starter condensation domain utilizes fatty acyl-CoA donors to acylate the Thr1 amino group and generate the fatty acyl-Thr1-S-pantetheinyl-GlbF intermediate to be used in subsequent chain elongation. Previously proposed to be mediated via acyl carrier protein fatty acid donors, direct utilization of fatty acyl-CoA donors for N-acylation of T-domain tethered amino acids is likely a common strategy for chain initiation in NRPS-mediated lipopeptide biosynthesis.