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Discovery of Glycosylated β-Amino Acid-Containing Macrolactams from Nonomuraea sp. 0L2P via Genome Mining.

Min Wang·Haoqing Zhang·Miao Cai·Nuo Chen·Liwei Liu
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Abstract

β-Amino acid-containing macrolactams (β-AACMs) are a class of bioactive natural products characterized by nitrogen-containing starter units within polyketide-derived macrocycles. Here, we report four previously undescribed macrolactams, gruelactams A-D (1-4), from Nonomuraea sp. 0L2P, discovered through an integrated approach combining genome mining, 15N-labeling, and antibacterial screening. Their planar structures were elucidated by comprehensive spectroscopic analyses, including 1D and 2D NMR and HRESI-MS, and their configurations were partially assigned based on ROESY data and bioinformatic analysis. Genome sequencing and antiSMASH analysis identified a putative type I polyketide synthase (PKS) biosynthetic gene cluster, enabling the proposal of a biosynthetic pathway. Bioactivity assays showed that gruelactam D (4) exhibits antibacterial activity against Bacillus cereus and Staphylococcus aureus, with MIC values of 8 and 16 μg/mL, respectively. These findings expand the chemical diversity of β-AACMs and demonstrate the utility of genome-guided approaches for discovering bioactive natural products from rare actinomycetes.

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Anti-Bacterial AgentsBacillus cereusAmino AcidsMultigene FamilyGlycosylationStaphylococcus aureusGenome, BacterialLactams, MacrocyclicActinobacteriaMicrobial Sensitivity TestsActinomycetalesLactamsPolyketide SynthasesBiological ProductsJournal Article

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Min Wang, Haoqing Zhang, Miao Cai, Nuo Chen, Liwei Liu. 2026-06-08. Discovery of Glycosylated β-Amino Acid-Containing Macrolactams from Nonomuraea sp. 0L2P via Genome Mining.. https://doi.org/10.1021/acschembio.5c00959

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