{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:39:33Z","timestamp":1792395573148,"version":"4.4.0"},"reference-count":70,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>De novo<\/jats:italic>\n                    biosynthesis of 4\u2010vinylcatechol (VCAT), a valuable bio\u2010based monomer and potent antioxidant, has emerged as a crucial objective due to its profound industrial and pharmacological significance. However, its biosynthesis is frequently hindered by limited precursor availability. In this study, we developed a highly efficient, dual\u2010plasmid platform utilizing engineered\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    cell factories to synthesize VCAT directly from glucose without precursor feeding. To establish optimal production cells, we evaluated combinations of different host strains and phenolic acid decarboxylase (\n                    <jats:italic>PAD<\/jats:italic>\n                    ) sources. Our results indicate that BL21(DE3) is less suitable for efficient\n                    <jats:italic>de novo<\/jats:italic>\n                    VCAT biosynthesis under the conditions tested. In contrast, the rpoA14(DE3), featuring a reprogrammed shikimate pathway, provided a more favorable host for VCAT production and enabled endogenous tyrosine supply, thereby eliminating the need for exogenous tyrosine supplementation required in BL21(DE3). To maximize this enhanced intracellular flux, we comparatively evaluated\n                    <jats:italic>padC<\/jats:italic>\n                    genes from different\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    strains. Comparative analysis demonstrated that the rpoA14(DE3)\u201010A5 exhibited significantly superior production titers, markedly outperforming both its 168\u2010PAD counterpart and the standard BL21(DE3) expression hosts. Cultivated in single\u2010step, aqueous fermentation at mild conditions, this optimal host\u2013enzyme combination achieved\n                    <jats:italic>de novo<\/jats:italic>\n                    accumulation of 200\u2009mg\/L VCAT, promising scalable biosynthesis.\n                  <\/jats:p>","DOI":"10.1002\/bit.70414","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T06:42:36Z","timestamp":1792392156000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering 4\u2010Vinylcatechol Biosynthesis in\n                    <i>Escherichia coli<\/i>\n                    Through Host\u2013Enzyme Combination"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-0538","authenticated-orcid":false,"given":"Esra","family":"Kaynak","sequence":"first","affiliation":[{"name":"Gebze Technical University, Faculty of Science Molecular Biology and Genetics Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7734-9978","authenticated-orcid":false,"given":"Merve","family":"Seven","sequence":"additional","affiliation":[{"name":"Yeditepe University, Faculty of Engineering and Natural Sciences Department of Genetics and Bioengineering Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8778-4586","authenticated-orcid":false,"given":"H\u00fcseyin","family":"Balc\u0131","sequence":"additional","affiliation":[{"name":"Gebze Technical University, Faculty of Science Molecular Biology and Genetics Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7217-3347","authenticated-orcid":false,"given":"Arzu","family":"Aysan","sequence":"additional","affiliation":[{"name":"Gebze Technical University, Faculty of Science Molecular Biology and Genetics Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattheos A. G.","family":"Koffas","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering Rensselaer Polytechnic Institute Troy NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7923-3031","authenticated-orcid":false,"given":"H\u00fclya","family":"Akdemir","sequence":"additional","affiliation":[{"name":"Gebze Technical University, Faculty of Science Molecular Biology and Genetics Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,18]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.ymben.2019.05.008","article-title":"Production of Pyranoanthocyanins Using Escherichia coli Co\u2010Cultures","volume":"55","author":"Akdemir H.","year":"2019","journal-title":"Metabolic Engineering"},{"issue":"1","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","DOI":"10.1080\/14686996.2025.2467617","article-title":"Formulation of Catechol\u2010Containing Adhesives for Enhanced Underwater Bonding and Workability","volume":"26","author":"Atencio\u2010Martinez C. 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D.","year":"2023","journal-title":"Biocatalysis and Agricultural Biotechnology"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.12991\/jrespharm.1797864"},{"key":"e_1_2_9_17_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.cbi.2025.111477","article-title":"Potent Inhibition of Human Monoamine Oxidase A and B by Phenolic Compounds and Polyunsaturated Fatty Acids in Tobacco Smoke","volume":"413","author":"Hong S. W.","year":"2025","journal-title":"Chemico\u2010Biological Interactions"},{"issue":"12","key":"e_1_2_9_18_1","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1007\/s00253-014-6313-3","article-title":"An Organic Solvent\u2010Tolerant Phenolic Acid Decarboxylase From Bacillus Licheniformis for the Efficient Bioconversion of Hydroxycinnamic Acids to Vinyl Phenol Derivatives","volume":"99","author":"Hu H.","year":"2015","journal-title":"Applied Microbiology and Biotechnology"},{"issue":"12","key":"e_1_2_9_19_1","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1002\/bit.24988","article-title":"Caffeic Acid Production Enhancement by Engineering a Phenylalanine Over\u2010Producing Escherichia coli Strain","volume":"110","author":"Huang Q.","year":"2013","journal-title":"Biotechnology and Bioengineering"},{"issue":"1","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/0378-1119(90)90336-P","article-title":"High Efficiency Transformation of Escherichia coli With Plasmids","volume":"96","author":"Inoue H.","year":"1990","journal-title":"Gene"},{"issue":"4","key":"e_1_2_9_21_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s00449-025-03128-2","article-title":"Metabolic Engineering of Escherichia Coli for Enhanced Production of P\u2010Coumaric Acid via L\u2010Phenylalanine Biosynthesis Pathway","volume":"48","author":"Jeong C.","year":"2025","journal-title":"Bioprocess and Biosystems Engineering"},{"issue":"47","key":"e_1_2_9_22_1","doi-asserted-by":"crossref","first-page":"10280","DOI":"10.1021\/acs.jafc.5b02423","article-title":"Effects of Caffeic Acid Phenethyl Ester and 4\u2010vinylcatechol on the Stabilities of Oil\u2010In\u2010Water Emulsions of Stripped Soybean Oil","volume":"63","author":"Jia C. 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Y.","year":"2015","journal-title":"Microbial Cell Factories"},{"issue":"8","key":"e_1_2_9_27_1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1021\/jf404850a","article-title":"Degradation of Caffeic Acid in Subcritical Water and Online HPLC\u2010DPPH Assay of Degradation Products","volume":"62","author":"Khuwijitjaru P.","year":"2014","journal-title":"Journal of Agricultural and Food Chemistry"},{"issue":"10","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1002\/bit.26797","article-title":"Metabolic Engineering of Escherichia coli for the Enhanced Production of L\u2010Tyrosine","volume":"115","author":"Kim B.","year":"2018","journal-title":"Biotechnology and Bioengineering"},{"issue":"4","key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1080\/01480545.2018.1492604","article-title":"Conflicting Actions of 4\u2010vinylcatechol in Rat Lymphocytes Under Oxidative Stress Induced by Hydrogen Peroxide","volume":"43","author":"Kishida T.","year":"2020","journal-title":"Drug and Chemical Toxicology"},{"issue":"7","key":"e_1_2_9_30_1","doi-asserted-by":"crossref","first-page":"2061","DOI":"10.1007\/s12010-021-03522-y","article-title":"Bioproduction of 4\u2010vinylphenol and 4\u2010vinylguaiacol \u03b2\u2010primeverosides Using Transformed Bamboo Cells Expressing Bacterial Phenolic Acid Decarboxylase","volume":"193","author":"Kitaoka N.","year":"2021","journal-title":"Applied Biochemistry and Biotechnology"},{"issue":"3","key":"e_1_2_9_31_1","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1021\/acs.macromol.2c02499","article-title":"Increasing the Scale and Decreasing the Cost of Making a Catechol\u2010Containing Adhesive Polymer","volume":"56","author":"Lancelot A.","year":"2023","journal-title":"Macromolecules"},{"issue":"8","key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1021\/acssynbio.3c00206","article-title":"Identifying, Characterizing, and Engineering a Phenolic Acid\u2010Responsive Transcriptional Factor From Bacillus Amyloliquefaciens","volume":"12","author":"Li C.","year":"2023","journal-title":"ACS Synthetic Biology"},{"issue":"1","key":"e_1_2_9_33_1","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12896-021-00705-7","article-title":"Improving the Catalytic Characteristics of Phenolic Acid Decarboxylase From Bacillus Amyloliquefaciens by the Engineering of N\u2010Terminus and C\u2010Terminus","volume":"21","author":"Li Q.","year":"2021","journal-title":"BMC Biotechnology"},{"issue":"17","key":"e_1_2_9_34_1","doi-asserted-by":"crossref","first-page":"7853","DOI":"10.1007\/s00253-013-5072-x","article-title":"Sensitivity to Vinyl Phenol Derivatives Produced by Phenolic Acid Decarboxylase Activity in Escherichia coli and Several Food\u2010Borne Gram\u2010Negative Species","volume":"97","author":"Licandro\u2010Seraut H.","year":"2013","journal-title":"Applied Microbiology and Biotechnology"},{"issue":"1","key":"e_1_2_9_35_1","doi-asserted-by":"crossref","first-page":"4976","DOI":"10.1038\/s41467-019-12961-5","article-title":"Rewiring Carbon Metabolism in Yeast for High Level Production of Aromatic Chemicals","volume":"10","author":"Liu Q.","year":"2019","journal-title":"Nature Communications"},{"issue":"4","key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1039\/D3GC03763K","article-title":"Biotransformation of Lignin into 4\u2010vinylphenol Derivatives Toward Lignin Valorization","volume":"26","author":"Liu R. Y.","year":"2024","journal-title":"Green Chemistry"},{"issue":"1","key":"e_1_2_9_37_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1186\/s13068-023-02425-w","article-title":"Challenges and Advances in Biotechnological Approaches for the Synthesis of Canolol and Other Vinylphenols From Biobased P\u2010Hydroxycinnamic Acids: A Review","volume":"16","author":"Lomascolo A.","year":"2023","journal-title":"Biotechnology for Biofuels and Bioproducts"},{"issue":"13","key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.3390\/foods14132187","article-title":"Biotransformation of Phenolic Acids in Foods: Pathways, Key Enzymes, and Technological Applications","volume":"14","author":"Lu C.","year":"2025","journal-title":"Foods"},{"key":"e_1_2_9_39_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107550","article-title":"C3G Improves Lipid Droplet Accumulation in the Proximal Tubules of High\u2010Fat Diet\u2010Induced Org Mice","volume":"211","author":"Lu Y.\u2010P.","year":"2025","journal-title":"Pharmacological Research"},{"key":"e_1_2_9_40_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.foodchem.2025.143532","article-title":"Flavor Perception and Biological Activities of Bitter Compounds in Food","volume":"477","author":"Luo T.","year":"2025","journal-title":"Food Chemistry"},{"issue":"1","key":"e_1_2_9_41_1","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00253-006-0792-9","article-title":"L\u2010Tyrosine Production by Deregulated Strains of Escherichia coli","volume":"75","author":"L\u00fctke\u2010Eversloh T.","year":"2007","journal-title":"Applied Microbiology and Biotechnology"},{"issue":"4","key":"e_1_2_9_42_1","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s11157-014-9348-0","article-title":"Transformation of Ferulic Acid to 4\u2010vinyl Guaiacol as a Major Metabolite: A Microbial Approach","volume":"13","author":"Mishra S.","year":"2014","journal-title":"Reviews in Environmental Science and Bio\/Technology"},{"issue":"14","key":"e_1_2_9_43_1","doi-asserted-by":"crossref","DOI":"10.3390\/molecules25143142","article-title":"Monitoring Hydroxycinnamic Acid Decarboxylation by Lactic Acid Bacteria Using High\u2010Throughput UV\u2010Vis Spectroscopy","volume":"25","author":"Miyagusuku\u2010Cruzado G.","year":"2020","journal-title":"Molecules"},{"issue":"1","key":"e_1_2_9_44_1","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms8010026","article-title":"Biotransformation of Monocyclic Phenolic Compounds by Bacillus Licheniformis TAB7","volume":"8","author":"Mpofu E.","year":"2019","journal-title":"Microorganisms"},{"issue":"7","key":"e_1_2_9_45_1","doi-asserted-by":"crossref","DOI":"10.3390\/molecules28073221","article-title":"An Overview of Bioactive Phenolic Molecules and Antioxidant Properties of Beer: Emerging Trends","volume":"28","author":"Nardini M.","year":"2023","journal-title":"Molecules"},{"issue":"4","key":"e_1_2_9_46_1","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms5040067","article-title":"A Two\u2010Step Bioconversion Process for Canolol Production From Rapeseed Meal Combining An Aspergillus Niger Feruloyl Esterase and the Fungus Neolentinus Lepideus","volume":"5","author":"Odinot E.","year":"2017","journal-title":"Microorganisms"},{"issue":"1","key":"e_1_2_9_47_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s13562-018-0466-6","article-title":"Substrate Specificity of the Phenolic Acid Decarboxylase From Lactobacillus Plantarum and Related Bacteria Analyzed by Molecular Dynamics and Docking","volume":"28","author":"Parada\u2010Fabi\u00e1n J. 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