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- Title
Advances in the adenylation domain: discovery of diverse non-ribosomal peptides.
- Authors
Xu, Delei; Zhang, Zihan; Yao, Luye; Wu, LingTian; Zhu, Yibo; Zhao, Meilin; Xu, Hong
- Abstract
Non-ribosomal peptide synthetases are mega-enzyme assembly lines that synthesize many clinically useful compounds. As a gatekeeper, they have an adenylation (A)-domain that controls substrate specificity and plays an important role in product structural diversity. This review summarizes the natural distribution, catalytic mechanism, substrate prediction methods, and in vitro biochemical analysis of the A-domain. Taking genome mining of polyamino acid synthetases as an example, we introduce research on mining non-ribosomal peptides based on A-domains. We discuss how non-ribosomal peptide synthetases can be engineered based on the A-domain to obtain novel non-ribosomal peptides. This work provides guidance for screening non-ribosomal peptide-producing strains, offers a method to discover and identify A-domain functions, and will accelerate the engineering and genome mining of non-ribosomal peptide synthetases. Key points: • Introducing adenylation domain structure, substrate prediction, and biochemical analysis methods • Advances in mining homo polyamino acids based on adenylation domain analysis • Creating new non-ribosomal peptides by engineering adenylation domains
- Subjects
NONRIBOSOMAL peptide synthetases; PEPTIDES; MINING engineering; GENOME editing; TRANSFER RNA; ASSEMBLY line methods; RIBOSOMAL DNA
- Publication
Applied Microbiology & Biotechnology, 2023, Vol 107, Issue 13, p4187
- ISSN
0175-7598
- Publication type
Article
- DOI
10.1007/s00253-023-12585-2