Investigation of Penicillin Binding Protein (PBP)-like Peptide Cyclase and Hydrolase in Surugamide Non-ribosomal Peptide Biosynthesis

Yongjun Zhou, Xiao Lin, Chunmin Xu, Yaoyao Shen, Shu-Ping Wang, Hongze Liao, Lei Li, Hai Deng (Corresponding Author), Hou-Wen Lin (Corresponding Author)

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)737-744
Number of pages8
JournalCell chemical biology
Volume26
Issue number5
Early online date21 Mar 2019
DOIs
Publication statusPublished - 16 May 2019

Fingerprint

Nucleic Acid-Independent Peptide Biosynthesis
Peptide Synthases
Penicillin-Binding Proteins
Peptide Hydrolases
Cyclic Peptides
Peptides
Enzymes
Site-Directed Mutagenesis
Computational Biology
Bacteria
Amino Acids

Keywords

  • penicillin binding protein
  • non-ribosomal peptide biosynthesis
  • cyclase and hydrolase
  • surugamides
  • GENE-CLUSTER
  • BETA-LACTAMASE
  • POLYKETIDE
  • LOGIC
  • CYCLIZATION

ASJC Scopus subject areas

  • Drug Discovery
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Clinical Biochemistry
  • Pharmacology

Cite this

Investigation of Penicillin Binding Protein (PBP)-like Peptide Cyclase and Hydrolase in Surugamide Non-ribosomal Peptide Biosynthesis. / Zhou, Yongjun; Lin, Xiao; Xu, Chunmin; Shen, Yaoyao; Wang, Shu-Ping; Liao, Hongze; Li, Lei; Deng, Hai (Corresponding Author); Lin, Hou-Wen (Corresponding Author).

In: Cell chemical biology, Vol. 26, No. 5, 16.05.2019, p. 737-744.

Research output: Contribution to journalArticle

Zhou, Yongjun ; Lin, Xiao ; Xu, Chunmin ; Shen, Yaoyao ; Wang, Shu-Ping ; Liao, Hongze ; Li, Lei ; Deng, Hai ; Lin, Hou-Wen. / Investigation of Penicillin Binding Protein (PBP)-like Peptide Cyclase and Hydrolase in Surugamide Non-ribosomal Peptide Biosynthesis. In: Cell chemical biology. 2019 ; Vol. 26, No. 5. pp. 737-744.
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