1. Academic Validation
  2. Biosynthesis and engineering of the nonribosomal peptides with a C-terminal putrescine

Biosynthesis and engineering of the nonribosomal peptides with a C-terminal putrescine

  • Nat Commun. 2023 Oct 19;14(1):6619. doi: 10.1038/s41467-023-42387-z.
Hanna Chen # 1 2 Lin Zhong # 3 Haibo Zhou # 1 Xianping Bai 1 Tao Sun 1 Xingyan Wang 1 Yiming Zhao 1 Xiaoqi Ji 1 Qiang Tu 3 Youming Zhang 1 3 Xiaoying Bian 4
Affiliations

Affiliations

  • 1 Helmholtz International Lab for Anti-infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, 266237, Qingdao, Shandong, China.
  • 2 School of Medicine, Linyi University, Shuangling Road, 276000, Linyi, China.
  • 3 CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055, Shenzhen, China.
  • 4 Helmholtz International Lab for Anti-infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, 266237, Qingdao, Shandong, China. bianxiaoying@sdu.edu.cn.
  • # Contributed equally.
Abstract

The broad bioactivities of nonribosomal Peptides rely on increasing structural diversity. Genome mining of the Burkholderiales strain Schlegelella brevitalea DSM 7029 leads to the identification of a class of dodecapeptides, glidonins, that feature diverse N-terminal modifications and a uniform putrescine moiety at the C-terminus. The N-terminal diversity originates from the wide substrate selectivity of the initiation module. The C-terminal putrescine moiety is introduced by the unusual termination module 13, the condensation domain directly catalyzes the assembly of putrescine into the peptidyl backbone, and other domains are essential for stabilizing the protein structure. Swapping of this module to another two nonribosomal peptide synthetases leads to the addition of a putrescine to the C-terminus of related nonribosomal Peptides, improving their hydrophilicity and bioactivity. This study elucidates the mechanism for putrescine addition and provides further insights to generate diverse and improved nonribosomal Peptides by introducing a C-terminal putrescine.

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