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Nanoconfinement addresses the challenge, yet the lack of tunable, flow\u2010compatible nanoreactors has limited exploration of extreme confinement matching the enzyme dimension under flow. Here, we reveal an enzyme\u2010scale confinement regime that maximizes enzymatic activity for flow reactions using enzyme\u2010encapsulating molecular network membrane reactors with nanometer\u2010scale pore tunability. Continuous\u2010flow kinetic resolution identifies an optimal balance at an enzyme\u2010to\u2010average pore size ratio of \u223c2, where confinement\u2010enhanced substrate access within sub\u2010minute space time is balanced against flow resistance. Under tight confinement, the apparent catalytic efficiency increases by up to 133\u2010fold relative to free enzymes and achieves 30\u00a0000\u2010fold higher specific space\u2010time yield than conventional flow reactors. This work presents a tunable nanoreactor platform and establishes enzyme\u2010scale confinement control as a key design principle for high\u2010performance nanofluidic biocatalysis in flow\u2010based synthesis and sensing.<\/jats:p>","DOI":"10.1002\/smll.202600066","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:30:36Z","timestamp":1780900236000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhanced Biocatalysis in Nanofluidic Membrane Reactors With Goldilocks Nanopores for Enzymes"],"prefix":"10.1002","volume":"22","author":[{"given":"Wangsuk","family":"Oh","sequence":"first","affiliation":[{"name":"School of Materials Science and Engineering Gwangju Institute of Science and Technology  Gwangju Republic of Korea"},{"name":"Department of Chemistry Yonsei University  Wonju Gangwon\u2010do Republic of 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