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Herein, we report a sol\u2010gel strategy to construct Pickering droplet derived microreactors (PDMRs) for the co\u2010confinement of enzymes and cofactors, which have been applied to continuous flow reactions without exogenous addition of cofactors. Within these self\u2010sufficient PDMRs, the cofactors are reversibly immobilized via electrostatic interactions, enabling in situ regeneration and free access to the enzyme. The PDMRs efficiently encapsulate enzymes and cofactors with 85\u2013100% immobilization efficiency and robust thermal stability. In PDMRs\u2010catalyzed continuous flow reactions, excellent catalytic performance and high cofactor total turnover number (TTN) were obtained in nicotinamide adenine dinucleotide phosphate (NADP\n                    <jats:sup>+<\/jats:sup>\n                    )\u2010dependent aldo\u2010keto reductase (AKR) catalyzed enantioselective reductions (80\u2013100% conversions, &gt;99% ee, 500\u00a0h stability, up to 173\u00a0907\u00a0mol mol\n                    <jats:sup>\u22121<\/jats:sup>\n                    TTN), and pyridoxal 5\u2010phosphate (PLP)\u2010dependent transaminase (TA) catalyzed enantioselective transaminations (80\u2013100% conversions, &gt;99% ee, 2\u00a0000\u00a0h stability, up to 45\u00a0552\u00a0mol mol\n                    <jats:sup>\u22121<\/jats:sup>\n                    TTN). Furthermore, the PDMRs are extended to the co\u2010confinement of a multi\u2010enzyme system (AKR and glucose dehydrogenase, GDH) with NADP\n                    <jats:sup>+<\/jats:sup>\n                    for chiral alcohols synthesis with sustained operational stability. This work establishes a potent and durable strategy for industrial\u2010scale continuous flow manufacturing.\n                  <\/jats:p>","DOI":"10.1002\/anie.202525681","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:14:48Z","timestamp":1774329288000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Co\u2010Confinement of Enzymes and Cofactors Within Pickering Droplet Derived Microreactors for Continuous Flow Catalysis"],"prefix":"10.1002","volume":"65","author":[{"given":"Min","family":"Fan","sequence":"first","affiliation":[{"name":"Engineering Research Center of the Ministry of Education for Fine Chemicals, Shanxi Key Laboratory of Coal\u2010based Value\u2010Added Chemicals Green Catalysis Synthesis Shanxi University  Taiyuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changhao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Applied Surface and Colloid Chemistry (MOE), School of Chemistry and Chemical Engineering Shaanxi Normal University Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7955-0512","authenticated-orcid":false,"given":"Hengquan","family":"Yang","sequence":"additional","affiliation":[{"name":"Engineering Research Center of the Ministry of Education for Fine Chemicals, Shanxi Key Laboratory of Coal\u2010based Value\u2010Added Chemicals Green Catalysis Synthesis Shanxi University  Taiyuan 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