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The biocatalytic cascade consisted of an oxidative deamination of <jats:sc>l<\/jats:sc>\u2010\u03b1\u2010amino acids by an <jats:sc>l<\/jats:sc>\u2010\u03b1\u2010amino acid deaminase from <jats:italic>Cosenzaea myxofaciens<\/jats:italic>, rendering 2\u2010oxoacid intermediates, with an ensuing aldol addition reaction to formaldehyde, catalyzed by metal\u2010dependent (<jats:italic>R<\/jats:italic>)\u2010 or (<jats:italic>S<\/jats:italic>)\u2010selective carboligases namely 2\u2010oxo\u20103\u2010deoxy\u2010<jats:sc>l<\/jats:sc>\u2010rhamnonate aldolase (YfaU) and ketopantoate hydroxymethyltransferase (KPHMT), respectively, furnishing 3\u2010substituted 4\u2010hydroxy\u20102\u2010oxoacids. The overall substrate conversion was optimized by balancing biocatalyst loading and amino acid and formaldehyde concentrations, yielding 36\u201398% aldol adduct formation and 91\u201398% ee for each enantiomer. Subsequent in\u2005situ follow\u2010up chemistry via hydrogen peroxide\u2010driven oxidative decarboxylation afforded the corresponding 2\u2010substituted 3\u2010hydroxycarboxylic acid derivatives.<\/jats:p><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/adsc202100145-toc-0001-m.png\"><jats:alt-text>magnified image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p>","DOI":"10.1002\/adsc.202100145","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T23:29:25Z","timestamp":1616455765000},"page":"2866-2876","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Chemoenzymatic Production of Enantiocomplementary 2\u2010Substituted 3\u2010Hydroxycarboxylic Acids from <scp>l<\/scp>\u2010\u03b1\u2010Amino Acids"],"prefix":"10.1002","volume":"363","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5207-3664","authenticated-orcid":false,"given":"Mathias","family":"Pickl","sequence":"first","affiliation":[{"name":"Department of Chemical Biology. 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