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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Engineered Biosynthesis through the Adenylation Domains from Nonribosomal Peptide Synthetases

Author(s): Zhenhua Lu, Xiao-Huan Liu, Xinsong Yuan, Fei Liu and Tao Wang*

Volume 23, Issue 20, 2023

Published on: 06 June, 2023

Page: [1973 - 1984] Pages: 12

DOI: 10.2174/1568026623666230601142757

Price: $65

Abstract

Nonribosomal peptide synthetases, consisted of multiple catalytic domains, are involved in the biosynthesis of an important family of bioactive natural products in a coordinated manner. Among the functional domains, adenylation domains are specifically responsible for recognizing carboxylic acid building blocks and synthesizing aminoacyl adenylates. Given their critical roles in the biosynthesis of the growing peptide, A-domains are also referred to as the “gatekeeper”. In this review, very recent developments on the A-domains from NRPSs are reviewed to expand the fundamental knowledge of the A domain, including knowledge on the structures, functions, and molecular interactions. Several recent examples were also discussed to highlight the great potential of A-domain engineering. This study should provide a framework for the combinatorial biosynthesis or synthetic biology-driven microbial production of novel nonribosomal peptides.

Keywords: Nonribosomal peptide synthetases, Adenylation domains, Domain engineering, Biosynthesis, biosynthetic engineering, Rational design.

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Graphical Abstract

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