News & ViewsPublished: 06 October 2026Metabolic engineeringKshitij Rai1,2 nAff5 &Caleb J. Bashor1,3,4 Nature Biotechnology (2026) Cite this articleSave articleView saved researchBy testing random combinations of genes at scale, shotgun genetic engineering enables discovery of new productive metabolic pathways in mammalian cells, including solutions for synthesizing two essential amino acids.This is a preview of subscription content, access via your institutionAccess options Access through your institutionAccess Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription27,99 € / 30 dayscancel any timeLearn moreSubscribe to this journalReceive 12 print issues and online access269,00 € per yearonly 22,42 € per issueLearn moreRent or buy this articlePrices vary by article typefrom$1.95to$39.95Learn morePrices may be subject to local taxes which are calculated during checkoutFig. 1: Shotgun genetic engineering streamlines the exploration of vast synthetic pathway design spaces.SubjectsExpression systemsMetabolic engineeringGenome Editing Techniques in Plant and Animal SystemsReferencesTrolle, J. et al. Nat. Biotechnol. https://doi.org/10.1038/s41587-026-03318-7 (2026).Article Google Scholar Petzold, C. J., Chan, L. J. G., Nhan, M. & Adams, P. D. Front. Bioeng. Biotechnol. 3, 135 (2015).Article PubMed PubMed Central Google Scholar Liberante, F. G. & Ellis, T. Curr. Opin. Syst. Biol. 25, 1–10 (2021).Article CAS Google Scholar Rai, K. & O’Connell, R. W. et al. Nature 650, 1035–1044 (2026).Article CAS PubMed Google Scholar Payne, S. H. & Loomis, W. F. Eukaryot. Cell 5, 272–276 (2006).Article CAS PubMed PubMed Central Google Scholar Trolle, J. et al. eLife 11, e72847 (2022).Article CAS PubMed PubMed Central Google Scholar Rai, K., Wang, Y., O’Connell, R. W., Patel, A. B. & Bashor, C. J. Curr. Opin. Biomed. Eng. 31, 100553 (2024).Article CAS Google Scholar Zhao, Y. et al. Nat. Biotechnol. 42, 1693–1704 (2024).Article CAS PubMed Google Scholar Wang, N. B., Beitz, A. M. & Galloway, K. E. Curr. Opin. Syst. Biol. 24, 18–31 (2020).Article PubMed PubMed Central Google Scholar Brixi, G. et al. Nature 652, 1349–1361 (2026).Article CAS PubMed PubMed Central Google Scholar Download referencesAuthor informationAuthor notesKshitij RaiPresent address: Department of Genome Sciences, University of Washington, Seattle, WA, USAAuthors and AffiliationsDepartment of Bioengineering, Rice University, Houston, TX, USAKshitij Rai & Caleb J. BashorGraduate Program in Systems, Synthetic and Physical Biology, Rice University, Houston, TX, USAKshitij RaiDepartment of Biosciences, Rice University, Houston, TX, USACaleb J. BashorRice Synthetic Biology Institute, Rice University, Houston, TX, USACaleb J. BashorAuthorsKshitij RaiView author publicationsSearch author on:PubMed Google ScholarCaleb J. BashorView author publicationsSearch author on:PubMed Google ScholarCorresponding authorCorrespondence to Caleb J. Bashor.Rights and permissionsReprints and permissionsAbout this article