Shikimate pathway-Dependent Catabolism: enabling near-to-maximum production yield of aromatics

Shikimate pathway-Dependent Catabolism: enabling near-to-maximum production yield of aromatics | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Shikimate pathway-Dependent Catabolism: enabling near-to-maximum production yield of aromatics Vitor Martins dos Santos, Lyon Bruinsma, Christos Batianis, Sara Moreno-Paz, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4761679/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Catabolism is a complex network of tightly regulated metabolic reactions that provides energy and carbon to fuel anabolism in all living organisms. Rewiring catabolism is essential for harnessing industrial biotechnology but remains a substantial metabolic engineering challenge due to its high genetic stability and tight regulation acquired through evolution. In this study, by combining metabolic modeling, rational engineering, and adaptive laboratory evolution, we fundamentally redesigned bacterial catabolism. We created a new-to-nature shikimate pathway-dependent catabolism (SDC) in the industrial bacterium Pseudomonas putida by reprogramming the shikimate pathway as the primary catabolic route instead of its native glycolytic one. SDC supports growth by supplying the glycerol catabolic end-product pyruvate, thereby enabling superior production of shikimate pathway-derived molecules. Through SDC, production of aromatics reached 89% of the pathway’s maximum theoretical yield, setting a new benchmark for their microbial synthesis. Our study successfully repurposed an anabolic pathway for catabolism, exemplifying the high metabolic plasticity of microbes and providing a bacterial chassis for the efficient production of fine and bulk chemicals. Biological sciences/Biotechnology/Metabolic engineering Biological sciences/Microbiology/Industrial microbiology Aromatics Shikimate pathway New-to-nature metabolism Adaptive laboratory evolution Growth-coupled design Full Text Additional Declarations Yes there is potential Competing Interest. L.B., C.B., S.P.M., and V.A.P.M.d.S. have filed a patent application related to the SDC technology. The patent application number is EP23210389.5. All other authors declare no competing interests. Supplementary Files SupplementaryData1.xlsx Dataset 1 SupplementaryData2.xlsx Dataset 2 SupplementaryData3.xlsx Dataset 3 SupplementaryData4.xlsx Dataset 4 SupplementaryData5.xlsx Dataset 5 SupplementaryData6.xlsx Dataset 6 SupplementaryData7.xlsx Dataset 7 SupplementaryInformation.pdf Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4761679","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":331528805,"identity":"3d5412a9-bea6-4c26-9922-f5629525fcdb","order_by":0,"name":"Vitor Martins dos 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