Authors: Xianping Bai, Lin Zhong, Yang Liu, Hanna Chen, Xingxing Shi, Xingyan Wang, Ruichen Xu, Qingsheng Yang, Xiaotong Diao, Shengying Li, Dalei Wu, Youming Zhang, Zhiyuan Li, Xiaoying Bian.
Journal: Journal of the American Chemical Society
DOI: 10.1021/jacs.6c01193
Link: https://pubs.acs.org/doi/10.1021/jacs.6c01193
Published: Feb, 18, 2026
Document Type: Research Article
Abstract:
Nonribosomal peptide synthetases (NRPSs) represent a valuable yet underexplored resource for producing bioactive natural products. However, most NRPSs remain silenced potentially due to factors such as dysfunction of the initiation unit. The starter condensation (Cs) domain of the initiation unit catalyzes the lipoinitiation of nonribosomal peptides via the incorporation of an N-terminal fatty acyl chain. The concept of initiation unit engineering introduced herein encompasses the replacement of the native initiation unit of NRPSs with a foreign and well-characterized Cs domain-containing initiation unit to activate the NRPS and optimize its expression. This strategy was employed herein to successfully access three of the six previously silent NRPS pathways in Mycetohabitans rhizoxinica HKI 454, a bacterium of the class β-proteobacteria, resulting in the identification of three classes of lipopeptides. This strategy …