Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases

Zhang, Mengli; Peng, Zijing; Huang, Zhenkuai; Fang, Jiaqi; Li, Xinhai; Qiu, Xiaoting

doi:10.3390/md22080349

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Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases

by

Mengli Zhang

,

Zijing Peng

,

Zhenkuai Huang

,

Jiaqi Fang

,

Xinhai Li

and

Xiaoting Qiu

^*

College of Food Science and Engineering, Ningbo University, Ningbo 315800, China

^*

Author to whom correspondence should be addressed.

Mar. Drugs 2024, 22(8), 349; https://doi.org/10.3390/md22080349

Submission received: 4 July 2024 / Revised: 23 July 2024 / Accepted: 27 July 2024 / Published: 29 July 2024

(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)

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Abstract

Nonribosomal peptides (NRPs) are biosynthesized by nonribosomal peptide synthetases (NRPSs) and are widely distributed in both terrestrial and marine organisms. Many NRPs and their analogs are biologically active and serve as therapeutic agents. The adenylation (A) domain is a key catalytic domain that primarily controls the sequence of a product during the assembling of NRPs and thus plays a predominant role in the structural diversity of NRPs. Engineering of the A domain to alter substrate specificity is a potential strategy for obtaining novel NRPs for pharmaceutical studies. On the basis of introducing the catalytic mechanism and multiple functions of the A domains, this article systematically describes several representative NRPS engineering strategies targeting the A domain, including mutagenesis of substrate-specificity codes, substitution of condensation-adenylation bidomains, the entire A domain or its subdomains, domain insertion, and whole-module rearrangements.

Keywords: adenylation domain in nonribosomal peptide synthetase; substrate-specificity codes of the adenylation domain; interrupted adenylation domain with methylase activity; nonribosomal peptide synthetase engineering targeting the adenylation domain

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MDPI and ACS Style

Zhang, M.; Peng, Z.; Huang, Z.; Fang, J.; Li, X.; Qiu, X. Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases. Mar. Drugs 2024, 22, 349. https://doi.org/10.3390/md22080349

AMA Style

Zhang M, Peng Z, Huang Z, Fang J, Li X, Qiu X. Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases. Marine Drugs. 2024; 22(8):349. https://doi.org/10.3390/md22080349

Chicago/Turabian Style

Zhang, Mengli, Zijing Peng, Zhenkuai Huang, Jiaqi Fang, Xinhai Li, and Xiaoting Qiu. 2024. "Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases" Marine Drugs 22, no. 8: 349. https://doi.org/10.3390/md22080349

APA Style

Zhang, M., Peng, Z., Huang, Z., Fang, J., Li, X., & Qiu, X. (2024). Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases. Marine Drugs, 22(8), 349. https://doi.org/10.3390/md22080349

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Functional Diversity and Engineering of the Adenylation Domains in Nonribosomal Peptide Synthetases

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