{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:37:35Z","timestamp":1790771855941,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100018822","name":"Western Sydney University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018822","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Efficient biocascades require integrated optimization of both biocatalysts and reaction conditions. In the present study, we employ a Latin hypercube sampling\u2013coupled Bayesian optimization (LHS\u2010BO) workflow to sequentially optimizes multivariate Zr\u2010based E\u2010MOF (E\u2010MOF = enzyme@metal\u2013organic framework biocomposite) design and the downstream glucose oxidase\u2013horseradish peroxidase (GOx\u2013HRP) biocascade. Enzymatic assays, attenuated total reflectance Fourier transform infrared spectroscopic (ATR\u2010FTIR) and ultraviolet\u2010visible (UV\u2010Vis) spectroscopic analyses confirm that the optimized multivariate E\u2010MOFs, ZG67, and ZH16, stabilize GOx and HRP in bioactive conformations. ZG67 and ZH16 achieve high encapsulation efficiency (92.2% \u00b1 0.7% and 90.2% \u00b1 1.3%), retained activity (87.1% \u00b1 2.2% and 102.9% \u00b1 14.9%), and enhanced stability under thermal (51.3% \u00b1 1.4% and 45.9% \u00b1 8.7%) and solvent treatments (&gt;80% and \u224860% residual activity, respectively, in ethanol or acetonitrile). The optimal GOx\u2013HRP cascade condition identified by LHS\u2010BO (R49) achieves over 95% of the theoretical maximum 2,3\u2010diaminophenazine (DAP) production rate predicted by the microkinetic model. The strong agreement amongst the experimental data, machine learning modeling, and kinetic modeling validates the robustness of this sequential E\u2010MOF optimization framework. This generalized LHS\u2010BO strategy provides a powerful tool for rational E\u2010MOF and multi\u2010enzyme cascade design, advancing biocatalysis and reaction engineering.<\/jats:p>","DOI":"10.1002\/smll.202512430","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T12:03:11Z","timestamp":1771329791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sequential Optimization of Multivariate Metal\u2013Organic Framework Based Biocatalysis"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3032-436X","authenticated-orcid":false,"given":"Weibin","family":"Liang","sequence":"first","affiliation":[{"name":"School of Science Western Sydney University  Penrith New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sisi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Roam Technologies  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross Andrew","family":"Shalliker","sequence":"additional","affiliation":[{"name":"School of Science Western Sydney University  Penrith New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Doonan","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Physics Chemistry and Earth Sciences University of Adelaide  Adelaide South Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Science Western Sydney University  Penrith New South Wales 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