TY - JOUR
T1 - Investigation of Penicillin Binding Protein (PBP)-like Peptide Cyclase and Hydrolase in Surugamide Non-ribosomal Peptide Biosynthesis
AU - Zhou, Yongjun
AU - Lin, Xiao
AU - Xu, Chunmin
AU - Shen, Yaoyao
AU - Wang, Shu-Ping
AU - Liao, Hongze
AU - Li, Lei
AU - Deng, Hai
AU - Lin, Hou-Wen
N1 - Copyright © 2019 Elsevier Ltd. All rights reserved.
PY - 2019/5/16
Y1 - 2019/5/16
N2 - Non-ribosomal peptides (NRPs) are biosynthesized on non-ribosomal peptides synthetase (NRPS) complexes, of which a C-terminal releasing domain commonly offloads the products. Interestingly, a dedicated releasing domain is absent in surugamides (SGM) NRPS, which directs the biosynthesis of cyclic octapeptides, SGM-A to -E, and the linear decapeptide, SGM-F. Here, we confirmed that surE is essential for the production of SGMs via genetic experiments. Biochemical characterization demonstrated that the recombinant enzyme, SurE, can generate the main products SGM-A and -F from the corresponding SNAC substrates, indicating that SurE is a standalone thioesterase-like enzyme. SurE also displays considerable substrate plasticity with expanded ring or different amino acid compositions to produce different cyclopeptides, highlighting the potential of chemoenzymatic applications. Site-directed mutagenesis allowed identification of the key residues of SurE. Finally, bioinformatics analysis suggested that SurE homologs are widely distributed in bacteria, suggesting a general mechanism of NRP release in Nature.
AB - Non-ribosomal peptides (NRPs) are biosynthesized on non-ribosomal peptides synthetase (NRPS) complexes, of which a C-terminal releasing domain commonly offloads the products. Interestingly, a dedicated releasing domain is absent in surugamides (SGM) NRPS, which directs the biosynthesis of cyclic octapeptides, SGM-A to -E, and the linear decapeptide, SGM-F. Here, we confirmed that surE is essential for the production of SGMs via genetic experiments. Biochemical characterization demonstrated that the recombinant enzyme, SurE, can generate the main products SGM-A and -F from the corresponding SNAC substrates, indicating that SurE is a standalone thioesterase-like enzyme. SurE also displays considerable substrate plasticity with expanded ring or different amino acid compositions to produce different cyclopeptides, highlighting the potential of chemoenzymatic applications. Site-directed mutagenesis allowed identification of the key residues of SurE. Finally, bioinformatics analysis suggested that SurE homologs are widely distributed in bacteria, suggesting a general mechanism of NRP release in Nature.
KW - penicillin binding protein
KW - non-ribosomal peptide biosynthesis
KW - cyclase and hydrolase
KW - surugamides
KW - GENE-CLUSTER
KW - BETA-LACTAMASE
KW - POLYKETIDE
KW - LOGIC
KW - CYCLIZATION
UR - http://www.mendeley.com/research/investigation-penicillin-binding-protein-pbplike-peptide-cyclase-hydrolase-surugamide-nonribosomal-p
UR - http://www.scopus.com/inward/record.url?scp=85065500772&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2019.02.010
DO - 10.1016/j.chembiol.2019.02.010
M3 - Article
C2 - 30905680
SN - 2451-9448
VL - 26
SP - 737
EP - 744
JO - Cell chemical biology
JF - Cell chemical biology
IS - 5
ER -