NosA catalyzing carboxyl-terminal amide formation in nosiheptide maturation via an enamine dealkylation on the serine-extended precursor peptide.
The carboxyl-terminal amide group has been often found in many bioactive peptide natural products, including nosiheptide belonging to the over 80 entity-containing thiopeptide family. Upon functional characterization of a novel protein NosA in nosiheptide biosynthesis, herein we report an unusual C-terminal amide forming strategy in general for maturating certain amide-terminated thiopeptides by processing their precursor peptides featuring a serine extension. NosA acts on an intermediate bearing a bis-dehydroalanine tail and catalyzes an enamide dealkylation to remove the acrylate unit originating from the extended serine residue.
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
Yi
Y
Yu
Heng
H
Guo
Qi
Q
Zhang
Lian
L
Duan
Ying
Y
Ding
Rijing
R
Liao
Chun
C
Lei
Ben
B
Shen
Wen
W
Liu
D000595:Amino Acid Sequence; D002384:Catalysis; D003640:Dealkylation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011498:Protein Precursors; D012694:Serine / Q000737:chemistry*; D013302:Streptomyces / Q000201:enzymology; D013844:Thiazoles / Q000737:chemistry
D011498:Protein Precursors; D013844:Thiazoles; D012694:Serine; C014134:nosiheptide