{
  "abstract": "Despite its industrial importance, microbial L-lysine production has largely been confined to classical producer strains, leaving the fast-growing, non-pathogenic marine bacterium V. natriegens mostly unexplored as an emerging biosynthetic platform. In this work, we established an L-lysine-overproducing V. natriegens DSM759 strain through a stepwise rational engineering strategy targeting the native biosynthetic pathway. Building on our prior systems-level analysis of the strain’s genetic and regulatory architecture, we identified key metabolic bottlenecks and targeted interventions to relieve them. The central intervention was relief of feedback inhibition on the two key regulatory enzymes, aspartate kinase (AK, lysC) and dihydrodipicolinate synthase (DHDPS, dapA). Transferring feedback resistance substitutions previously characterized in E. coli to conserved positions in the V. natriegens DSM759 enzymes produced L-lysine-insensitive variants with kinetic parameters comparable to the corresponding wild-type enzymes. Among the tested configurations, the strain co-expressing Vn.lysC2 and Vn.dapA1:E84T reached the highest L-lysine titer (9.0 ± 0.6 mM) and yield (0.11 ± 0.01 molLys molGlc−1), whereas overexpression of additional L-lysine pathway genes provided no further benefit. Exploiting the host’s substrate range, we further demonstrated L-lysine synthesis from the chitin-derived amino sugar N-acetylglucosamine (0.09 ± 0.00 molLys molGlcNAc−1), highlighting the potential to valorize chitin-rich waste streams from the seafood industry. This work establishes a minimal rational strategy for L-lysine biosynthesis in V. natriegens DSM759 and positions it as a candidate platform for sustainable amino acid production.\n\nKey points: • E. coli-derived rational engineering strategies were transferable to V. natriegens\n\n• Native pathway deregulation was sufficient to enable L-lysine production\n\n• Chitin-derived N-acetylglucosamine supports L-lysine synthesis\n\nSupplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s00253-026-14090-8.",
  "abstract_shown": true,
  "affiliations": [
    "Institute of Natural Materials Technology, TU Dresden, 01062 Dresden, Germany",
    "School of Molecular Sciences, The University of Western Australia, Crawley, 6009 Australia",
    "Forrest Research Foundation, Crawley, 6009 Australia",
    "Oceans Institute, The University of Western Australia, Crawley, 6009 Australia",
    "School of Chemistry and Life Science, Hanoi University of Science and Technology, 1 Dai Co Viet, Hanoi, Vietnam"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Elly Straube"
    },
    {
      "affs": [
        0
      ],
      "name": "Thi Van Anh Tran"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "Anna Faber"
    },
    {
      "affs": [
        0
      ],
      "name": "Nadine Ihle"
    },
    {
      "affs": [
        0
      ],
      "name": "Rubén Crespo Blanco"
    },
    {
      "affs": [
        4
      ],
      "name": "Ha Thanh Le"
    },
    {
      "affs": [
        1,
        3
      ],
      "name": "Georg Fritz"
    },
    {
      "affs": [
        0
      ],
      "name": "Cláudio J. R. Frazão"
    },
    {
      "affs": [
        0
      ],
      "name": "Thomas Walther"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fgn6afrfn7dpx.bib",
  "cited_by": 0,
  "doi": "10.1007/s00253-026-14090-8",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737242/",
  "id": "fgn6afrfn7dpx",
  "issns": [
    "0175-7598",
    "1432-0614"
  ],
  "landing_url": "https://doi.org/10.1007/s00253-026-14090-8",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "1312|Microbial Metabolic Engineering and Bioproduction"
    ]
  ],
  "openalex": "W7153860451",
  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s00253-026-14090-8.pdf",
  "pmcid": "PMC13737242",
  "pmid": "42980829",
  "published": "2026-11-04",
  "publisher": "Springer",
  "ris": "https://research.draconitic.com/paper/fgn6afrfn7dpx.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:29Z",
      "native_id": "PMC13737242",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s00253-026-14090-8"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Microbial Metabolic Engineering and Bioproduction",
      "subfield": "molecular-biology"
    }
  ],
  "title": "L-Lysine production from glucose and chitin monomers using engineered Vibrio natriegens",
  "title_text": "L-Lysine production from glucose and chitin monomers using engineered Vibrio natriegens",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:29Z",
  "url": "https://research.draconitic.com/paper/fgn6afrfn7dpx",
  "venue": "Applied Microbiology and Biotechnology",
  "versions": []
}