Activation of the pacidamycin PacL adenylation domain by MbtH-like proteins.
Nonribosomal peptide synthetase (NRPS) assembly lines are major avenues for the biosynthesis of a vast array of peptidyl natural products. Several hundred bacterial NRPS gene clusters contain a small (∼70-residue) protein belonging to the MbtH family for which no function has been defined. Here we show that two strictly conserved Trp residues in MbtH-like proteins contribute to stimulation of amino acid adenylation in some NRPS modules. We also demonstrate that adenylation can be stimulated not only by cognate MbtH-like proteins but also by homologues from disparate natural product pathways.
Zhang
Wenjun
W
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, United States.
Heemstra
John R
JR
Walsh
Christopher T
CT
Imker
Heidi J
HJ
D001426:Bacterial Proteins / Q000737:chemistry*; D005810:Multigene Family; D009169:Mycobacterium tuberculosis / Q000201:enzymology; D010453:Peptide Synthases / Q000737:chemistry*; D017434:Protein Structure, Tertiary
D001426:Bacterial Proteins; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase