ArticleNature communications2025
A rational multi-target combination strategy for synergistic improvement of non-ribosomal peptide production.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- Construction of a library of gene expression elements in industrialSynthetic and systems biotechnology · 2026Article
- Scalable secondary metabolite production in Streptomyces using a plug-and-play system.Nature biotechnology · 2026Article
- Systematic Engineering of Proteases in Saccharopolyspora Spinosa Reveals Synergistic Enhancement of Spinosad Biosynthesis via Substrate Flux Optimization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Potential of Non-Ribosomal Peptide Engineering for Creating New Antimicrobial Complexes.Molecules (Basel, Switzerland) · 2026Review
- Multiple active-sites editing of adenylation domains of srfA operon for constructing diverse surfactin lipopeptide.Communications biology · 2026Article
- Model-Guided Systematic Metabolic Engineering for Enhanced Spinosad Biosynthesis in Saccharopolyspora spinosa NHF132.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Astaxanthin Overproduction Enhanced by Metabolomics-Guided Rational Metabolic Engineering inACS synthetic biology · 2025Article
- Genomic Characterization of Four Novel Probiotic Strains with Enzymatic Activity and Their Effects on Carp (Animals : an open access journal from MDPI · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Non-ribosomal peptides (NRPs) are pharmaceutically important natural products that include numerous clinical drugs. However, the biosynthesis of these NRPs is intricately regulated and improving production through manipulation of multiple regulatory targets remains largely empirical. We here develop a screening-based, multi-target rational combination strategy and demonstrate its effectiveness in enhancing the titers of three NRP drugs - daptomycin, thaxtomin A and surfactin. Initially, we devise a reliable colorimetric analog co-expression and co-biosynthesis reporter system for screening high-yielding phenotypes. Subsequently, through coupling CRISPR interference to induce genome-wide differential expression, we identify dozens of repressors that inhibit the biosynthesis of these NRPs. To address the challenge of multi-target combination, we further developed a dual-target screen approach and introduced an interplay map based on the synergy coefficient of each pairwise interaction. Employing this strategy, we engineer the final strains with multi-target synergistic combination and achieve the titer improvement of the three NRPs. Our work provides a rational multi-target combination strategy for production improvement of NRPs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.