{
  "abstract": "Classical pathway metabolic engineering relies on enhancing strain productivity through the introduction of rationally identified genetic perturbations, which while useful, are time-consuming and miss unintuitive targets. Genome-wide CRISPR screens offer an alternative by efficiently sampling genomes, enabling the engineering of novel phenotypes, and are further enhanced when combined with high-throughput strain interrogation methods. Here, using Saccharomyces cerevisiae, we engineered small molecule biosensors into population enrichment tools using zeocin resistance and fluorescence as signal outputs. We then introduced the multi-functional genome-wide CRISPR (MAGIC) library that targets every gene for activation, interference, or deletion, thus creating biosensor-aided MAGIC, or senMAGIC. As a case study, we utilized senMAGIC to identify single genetic determinants that improve productivity of the nylon precursors protocatechuic and cis,cis-muconic acids (PCA and ccM). These were then randomly assembled as triple gRNA-tRNA arrays for multiplexed gene perturbations to identify combinatorial effects. Top gRNA hits were then confirmed using direct genomic integrations in senMAGIC-free production strains, resulting in identifying known as well as novel targets that increase PCA and ccM titres. Our results demonstrate senMAGIC as a robust automation-friendly whole-genome evolution tool and highlight limitations of the method, providing a roadmap for future multifunctional CRISPR screens to optimize host metabolism for efficient bioprocesses.",
  "abstract_shown": true,
  "affiliations": [
    "Concordia University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "M. A. Nasr"
    },
    {
      "name": "A. Knoops"
    },
    {
      "name": "M. Thornbury"
    },
    {
      "name": "M. Davies"
    },
    {
      "name": "D. H. Kwan"
    },
    {
      "name": "V. J. J. Martin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/26f50yrbdpxe7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.31.762157",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.762157v1.full",
  "id": "26f50yrbdpxe7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.762157v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "synthetic biology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.31.762157v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/26f50yrbdpxe7.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:21:14Z",
      "native_id": "10.64898/2026.10.31.762157",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.31.762157v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:synthetic biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Biosensor-guided genome-wide CRISPR screens enable cis,cis-muconic acid overproduction in yeast",
  "title_text": "Biosensor-guided genome-wide CRISPR screens enable cis,cis-muconic acid overproduction in yeast",
  "type": "preprint",
  "updated_at": "2026-11-05T00:20:43Z",
  "url": "https://research.draconitic.com/paper/26f50yrbdpxe7",
  "venue": "bioRxiv",
  "versions": []
}