Sourdough starter-inspired living materials grown from probiotic consortia with engineered division-of-labor | 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 Sourdough starter-inspired living materials grown from probiotic consortia with engineered division-of-labor Yong Lai, Shuchen Wang, Yiqi Xu, Yuewei Zhan, Martin Echavarria Galindo, and 12 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8285095/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 Synthetic genetic circuits, engineered networks of genetic components that perform user-defined logical functions in living cells, enable precise control over cellular behavior. As circuits become more complex to support sophisticated functions, implementing them within a single cell population becomes difficult. Tasks can instead be distributed among different populations in engineered consortia. However, selecting appropriate consortia and harnessing the natural traits of each species for such a division of labor remain unsolved challenges. Here, we report the creation of SINERGY, an engineered synthetic sourdough starter in which functional modules are distributed between the two constituent species. These modules, consisting of sensing, cross-kingdom communication, and response, enable in vitro biosensing and in vivo drug delivery and modulate the gut ecosystem in an animal disease model. SINERGY not only preserves the long-standing safety and health-promoting properties of the natural components but also endows symbiotic microbes with programmable functionalities, facilitating broad applications in biomedicine. Biological sciences/Microbiology/Microbial communities Biological sciences/Biotechnology/Molecular engineering/Synthetic biology Synthetic biology division of labor engineered living materials synthetic sourdough starter probiotic consortia GPCR biosensors cross-kingdom communication in situ drug delivery inflammatory bowel disease Full Text Additional Declarations Yes there is potential Competing Interest. Y.L. and S.W. are co-inventors on a US provisional patent application (no. 63/848307), which is based on discoveries described in this paper. T-C.T. is a cofounder and equity holder of Anthology. T.K.L. is a cofounder of Senti Biosciences, Synlogic, Engine Biosciences, Tango Therapeutics, Corvium, BiomX, Eligo Biosciences, Bota.Bio, Avendesora and NE47Bio. T.K.L. also holds financial interests in nest.bio, Armata, IndieBio, MedicusTek, Quark Biosciences, Personal Genomics, Thryve, Lexent Bio, March Therapeutics, Serotiny, Avendesora and Pulmobiotics. G.M.C has financial interests in Glottatech.com. Supplementary Files SupplementaryTable1.pdf Supplementary Table 1 SupplementaryTable2.pdf Supplementary Table 2 SINERGYSupplementaryFigs13NatureMicrobiologyFinal.pdf Supplementary Figures 1-3 SINERGYExtendedDataFigs110NatureMicrobiologyFinal.pdf Extended Data Figures 1-10 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-8285095","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":561924037,"identity":"39065c79-45f6-4efb-b48c-91f26fa8b373","order_by":0,"name":"Yong Lai","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtElEQVRIiWNgGAWjYLCCBwwSciCameEAsVoSGCSMQRpI0sKQ2EC0FoPjvYdfJNRYpG84f/4Ac8EZYrScOZdmkXBMInfDjWQG5hk3iNFyI8fMIIENpAXoMJ4PRGv5J5FucP4w8VqMHyS2SSQYHAA6jIcYh0meOWPGkNgnYTjzRrLBYR5ivM93vMf4w4dvdfJ85w8+fMxzjAgtCgcY2CRgnANEaGBgkAdGITF+HgWjYBSMgpEMAACtOupOq0uJAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-0208-4351","institution":"Hong Kong University of Science and Technology","correspondingAuthor":true,"prefix":"","firstName":"Yong","middleName":"","lastName":"Lai","suffix":""},{"id":561924038,"identity":"002db365-eb18-41cb-a41a-42ff5551c9e4","order_by":1,"name":"Shuchen Wang","email":"","orcid":"","institution":"Hong Kong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Shuchen","middleName":"","lastName":"Wang","suffix":""},{"id":561924039,"identity":"73111eac-95e5-463d-adb5-cfa570a46f3a","order_by":2,"name":"Yiqi Xu","email":"","orcid":"","institution":"Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University","correspondingAuthor":false,"prefix":"","firstName":"Yiqi","middleName":"","lastName":"Xu","suffix":""},{"id":561924040,"identity":"170343c5-acd8-4a9e-a9f5-367b91e9fcb5","order_by":3,"name":"Yuewei Zhan","email":"","orcid":"","institution":"Hong Kong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Yuewei","middleName":"","lastName":"Zhan","suffix":""},{"id":561924041,"identity":"2237aad6-5203-4ccd-84f6-4c7b6e9f5d15","order_by":4,"name":"Martin Echavarria Galindo","email":"","orcid":"","institution":"Hong Kong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"Echavarria","lastName":"Galindo","suffix":""},{"id":561924042,"identity":"fa41c183-f73e-4aca-af3c-08b7b19f68a5","order_by":5,"name":"Sherman Cheuk Yui Chau","email":"","orcid":"","institution":"Hong Kong University of Science and Technology","correspondingAuthor":false,"prefix":"","firstName":"Sherman","middleName":"Cheuk Yui","lastName":"Chau","suffix":""},{"id":561924043,"identity":"666dfbec-b1c1-4695-bc5b-2f2eaa24d0f6","order_by":6,"name":"Cui Liang","email":"","orcid":"https://orcid.org/0000-0001-9356-825X","institution":"Singapore-MIT Alliance for Research \u0026 Technology","correspondingAuthor":false,"prefix":"","firstName":"Cui","middleName":"","lastName":"Liang","suffix":""},{"id":561924044,"identity":"ac9cc8c5-b9af-4cde-a008-9aa35e33dd35","order_by":7,"name":"William Shaw","email":"","orcid":"","institution":"Biological Design Center, Boston University","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"","lastName":"Shaw","suffix":""},{"id":561924045,"identity":"58843ada-673b-4771-9de1-18c3ec338c96","order_by":8,"name":"Wen Jun Xie","email":"","orcid":"","institution":"University of Southern California","correspondingAuthor":false,"prefix":"","firstName":"Wen","middleName":"Jun","lastName":"Xie","suffix":""},{"id":561924046,"identity":"0417d467-81b3-4e89-a2b2-6c1687ad8367","order_by":9,"name":"Hor Yue Tan","email":"","orcid":"","institution":"Centre for Chinese Herbal Medicine Drug Development, Hong Kong Baptist University","correspondingAuthor":false,"prefix":"","firstName":"Hor","middleName":"Yue","lastName":"Tan","suffix":""},{"id":561924047,"identity":"f9dcc288-65c7-4062-ac75-4dba76f100e3","order_by":10,"name":"Chengyuan Lin","email":"","orcid":"","institution":"Hong Kong Baptist University","correspondingAuthor":false,"prefix":"","firstName":"Chengyuan","middleName":"","lastName":"Lin","suffix":""},{"id":561924048,"identity":"3f99c5c8-ccc3-4964-86b7-63872637d3d6","order_by":11,"name":"Xue Jiang","email":"","orcid":"","institution":"The University of Hong Kong","correspondingAuthor":false,"prefix":"","firstName":"Xue","middleName":"","lastName":"Jiang","suffix":""},{"id":561924049,"identity":"fc7fba33-957b-438a-8b47-9385fc70bd29","order_by":12,"name":"Zhaoxiang Bian","email":"","orcid":"","institution":"Hong Kong Baptist University","correspondingAuthor":false,"prefix":"","firstName":"Zhaoxiang","middleName":"","lastName":"Bian","suffix":""},{"id":561924050,"identity":"1a253f28-7f36-4762-8ef4-2220a5991cbc","order_by":13,"name":"Peter Dedon","email":"","orcid":"https://orcid.org/0000-0003-0011-3067","institution":"Massachusetts Institute of Technology","correspondingAuthor":false,"prefix":"","firstName":"Peter","middleName":"","lastName":"Dedon","suffix":""},{"id":561924051,"identity":"d709d4af-d586-4fc6-b254-7bdb04e0e033","order_by":14,"name":"George Church","email":"","orcid":"https://orcid.org/0000-0001-6232-9969","institution":"Harvard University","correspondingAuthor":false,"prefix":"","firstName":"George","middleName":"","lastName":"Church","suffix":""},{"id":561924052,"identity":"25912991-82ba-4fca-976b-e893fcef2c02","order_by":15,"name":"Timothy Lu","email":"","orcid":"https://orcid.org/0000-0002-3918-8923","institution":"Massachusetts Institute of Technology","correspondingAuthor":false,"prefix":"","firstName":"Timothy","middleName":"","lastName":"Lu","suffix":""},{"id":561924053,"identity":"2a6afd56-2516-4867-b01d-a56cde4a7dc0","order_by":16,"name":"Tzu-Chieh Tang","email":"","orcid":"https://orcid.org/0000-0002-6215-8714","institution":"Harvard University","correspondingAuthor":false,"prefix":"","firstName":"Tzu-Chieh","middleName":"","lastName":"Tang","suffix":""}],"badges":[],"createdAt":"2025-12-05 07:35:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8285095/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8285095/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":98627878,"identity":"c6479abf-dd9c-4781-83dc-03284788a4e3","added_by":"auto","created_at":"2025-12-19 17:10:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2355239,"visible":true,"origin":"","legend":"Article File","description":"","filename":"SINERGYManuscriptNatureMicrobiologyFinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8285095/v1_covered_5ccafdb4-3ae6-4b62-a723-c6aebb087948.pdf"},{"id":98578901,"identity":"c3f5822b-7ce2-4b14-bf20-6dd2af8101af","added_by":"auto","created_at":"2025-12-19 08:07:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":56470,"visible":true,"origin":"","legend":"Supplementary Table 1","description":"","filename":"SupplementaryTable1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8285095/v1/871382d3aef377b1672cb3ac.pdf"},{"id":98578900,"identity":"3068b991-2cb1-4448-a08d-35defa08309c","added_by":"auto","created_at":"2025-12-19 08:07:16","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":14075,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary Table 2\u003c/p\u003e","description":"","filename":"SupplementaryTable2.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8285095/v1/7acc39193c177bb6726f4de9.pdf"},{"id":98578902,"identity":"d318b1ee-0c6e-44fc-93dc-05d3a3afaa8b","added_by":"auto","created_at":"2025-12-19 08:07:16","extension":"pdf","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":1147560,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary Figures 1-3\u003c/p\u003e","description":"","filename":"SINERGYSupplementaryFigs13NatureMicrobiologyFinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8285095/v1/4f8b842ed124a4ba7271f39a.pdf"},{"id":98578903,"identity":"b0d9507c-3a77-4dba-a055-3c5f08d67f3e","added_by":"auto","created_at":"2025-12-19 08:07:16","extension":"pdf","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":5669342,"visible":true,"origin":"","legend":"Extended Data Figures 1-10","description":"","filename":"SINERGYExtendedDataFigs110NatureMicrobiologyFinal.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8285095/v1/576f890d3fb61ebf483fdb02.pdf"}],"financialInterests":"\u003cb\u003eYes\u003c/b\u003e there is potential Competing Interest.\nY.L. and S.W. are co-inventors on a US provisional patent application (no. 63/848307), which is based on discoveries described in this paper. T-C.T. is a cofounder and equity holder of Anthology. T.K.L. is a cofounder of Senti Biosciences, Synlogic, Engine Biosciences, Tango Therapeutics, Corvium, BiomX, Eligo Biosciences, Bota.Bio, Avendesora and NE47Bio. T.K.L. also holds financial interests in nest.bio, Armata, IndieBio, MedicusTek, Quark Biosciences, Personal Genomics, Thryve, Lexent Bio, March Therapeutics, Serotiny, Avendesora and Pulmobiotics. G.M.C has financial interests in Glottatech.com.","formattedTitle":"Sourdough starter-inspired living materials grown from probiotic consortia with engineered division-of-labor","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"
[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Synthetic biology, division of labor, engineered living materials, synthetic sourdough starter, probiotic consortia, GPCR biosensors, cross-kingdom communication, in situ drug delivery, inflammatory bowel disease","lastPublishedDoi":"10.21203/rs.3.rs-8285095/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8285095/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Synthetic genetic circuits, engineered networks of genetic components that perform user-defined logical functions in living cells, enable precise control over cellular behavior. As circuits become more complex to support sophisticated functions, implementing them within a single cell population becomes difficult. Tasks can instead be distributed among different populations in engineered consortia. However, selecting appropriate consortia and harnessing the natural traits of each species for such a division of labor remain unsolved challenges. Here, we report the creation of SINERGY, an engineered synthetic sourdough starter in which functional modules are distributed between the two constituent species. These modules, consisting of sensing, cross-kingdom communication, and response, enable in vitro biosensing and in vivo drug delivery and modulate the gut ecosystem in an animal disease model. SINERGY not only preserves the long-standing safety and health-promoting properties of the natural components but also endows symbiotic microbes with programmable functionalities, facilitating broad applications in biomedicine.","manuscriptTitle":"Sourdough starter-inspired living materials grown from probiotic consortia with engineered division-of-labor","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-19 08:07:07","doi":"10.21203/rs.3.rs-8285095/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"
[email protected]","identity":"nature-microbiology","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"nmicrobiol","sideBox":"Learn more about [Nature Microbiology](http://www.nature.com/nmicrobiol/)","snPcode":"","submissionUrl":"","title":"Nature Microbiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Research","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"bfc39745-32be-4c84-b623-8d90b38edd30","owner":[],"postedDate":"December 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":59838138,"name":"Biological sciences/Microbiology/Microbial communities"},{"id":59838139,"name":"Biological sciences/Biotechnology/Molecular engineering/Synthetic biology"}],"tags":[],"updatedAt":"2026-02-19T08:00:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-19 08:07:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8285095","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8285095","identity":"rs-8285095","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}
Text is read by the "Ask this paper" AI Q&A widget below.
Extraction quality varies by source — PMC NXML preserves structure
cleanly, OA-HTML may include some navigation residue, and OA-PDF can
have broken hyphenation. The publisher copy
(via DOI)
is the canonical version.