ArticleJournal of the American Chemical Society2025
Logical Exploration of Cinnamoyl-Containing Nonribosomal Peptides via Metabologenomic Targeting and Regulator Overexpression.
Article in Journal of the American Chemical Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- The PreKit platform: Cryptic gene clusters activation and high-titer compound production.Synthetic and systems biotechnology · 2026Article
- Structural determination of natural products at speeds and scale of high-throughput screening.Natural product reports · 2026Review
- Targeted Discovery of β‑Branched Conjugated Polyketides from Bacteria Based on Genomic and Metabolomic Hallmarks.JACS Au · 2026Article
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Authors and funding
15 authors.
Funding
Abstract
A targeted method for discovering cinnamoyl-containing nonribosomal peptides (CCNPs), a unique class of bioactive compounds, was devised by using cinnamoyl isomerase, a key enzyme in the biosynthesis of the cinnamoyl moiety, as a genome mining probe. A total of 39 hit strains were obtained, including 35 from polymerase chain reaction-based screening of the in-house bacterial library (2.5% of 1400 strains) targeting the cinnamoyl isomerase-encoding gene and 4 from the genome mining of online databases. Sequence similarity networking and phylogenetic analyses of the isomerase amplicons (∼530 bp) classified the CCNPs into three major substructure-based groups (Z-, E-, and M-type CCNPs) and revealed distinct clade-structure relationships (13 clades). To overcome the challenge of silent biosynthetic gene clusters, we activated these clusters by overexpressing conserved cluster-situated LuxR regulators combined with extensive culture optimization. CCNP production was metabolomically detected in the bacterial extracts by using the characteristic UV absorption and MS/MS fragments of cinnamoyl moieties. CCNP production was observed in 20 of the 39 hit strains, resulting in the isolation of 6 new CCNPs, including oxy-skyllamycin B (
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