{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:00:10Z","timestamp":1787590810358,"version":"build-2736575974"},"reference-count":69,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T00:00:00Z","timestamp":1757980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp; Bioengineering"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Streptomyces leeuwenhoekii<\/jats:italic>\n                    C34\n                    <jats:sup>T<\/jats:sup>\n                    produces the polyketides chaxamycins A\u2013D and chaxalactins A\u2013C. The former metabolites exhibit antibiotic activity and antitumoral properties. In this study, we selected a subset of overexpression targets, predicted using the FSEOF algorithm, to increase chaxamycin production based on the\n                    <jats:italic>i<\/jats:italic>\n                    VR1007 genome\u2010scale model (GEM). Eight genes were individually cloned under strong constitutive promoters and introduced into the genome of\n                    <jats:italic>S. leeuwenhoekii<\/jats:italic>\n                    C34\n                    <jats:sup>T<\/jats:sup>\n                    , including\n                    <jats:italic>ugp<\/jats:italic>\n                    ,\n                    <jats:italic>tkt<\/jats:italic>\n                    ,\n                    <jats:italic>tal<\/jats:italic>\n                    , and the\n                    <jats:italic>acc<\/jats:italic>\n                    complex, giving rise to strains S1\u2013S8. The production of chaxamycins by these engineered strains was compared to the wild\u2010type and to a strain overexpressing the pcc complex (S9) (not predicted as target by the model). Chaxamycins were detected in all the samples, with higher amounts observed in strains S1 through S8. In contrast, strain S9 did not show improved chaxamycin A\u2013C production. The best results were obtained with strain\n                    <jats:italic>tkt<\/jats:italic>\n                    (S2),\n                    <jats:italic>tal<\/jats:italic>\n                    (S3), and\n                    <jats:italic>mcm\/mce<\/jats:italic>\n                    (S8), which demonstrated 7.41\u2010, 3.67\u2010, and 3.33\u2010fold increases in total chaxamycin production, respectively. These strains overexpress genes associated with AHBA synthesis, pentose phosphate pathway or (2S)\u2010methyl\u2010malonyl\u2010CoA biosynthesis. Extracts from higher producers also showed higher bioactivity against\n                    <jats:italic>Micrococcus luteus<\/jats:italic>\n                    . Thus, the predictions made using the iVR1007 model, were successfully applied to increase chaxamycin production, further validating the utility of the FSEOF algorithm for predicting metabolic engineering targets.\n                  <\/jats:p>","DOI":"10.1002\/bit.70067","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T12:14:44Z","timestamp":1758024884000},"page":"3376-3392","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Metabolic Engineering of\n                    <i>Streptomyces leeuwenhoekii<\/i>\n                    C34\n                    <sup>T<\/sup>\n                    to Increase Chaxamycin Production Based on the\n                    <i>i<\/i>\n                    VR1007 Genome\u2010Scale Model"],"prefix":"10.1002","volume":"122","author":[{"given":"Anett","family":"Rubio","sequence":"first","affiliation":[{"name":"Department of Chemical Engineering, Biotechnology, and Materials, Centre for Biotechnology and Bioengineering (CeBiB) University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2463-4820","authenticated-orcid":false,"given":"Valeria","family":"Razmilic","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Biotechnology, and Materials, Centre for Biotechnology and Bioengineering (CeBiB) University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Brain\u2010Isasi","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Biotechnology, and Materials, Centre for Biotechnology and Bioengineering (CeBiB) University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Biotechnology, and Materials, Centre for Biotechnology and Bioengineering (CeBiB) University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3475-7664","authenticated-orcid":false,"given":"Juan A.","family":"Asenjo","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering, Biotechnology, and Materials, Centre for Biotechnology and Bioengineering (CeBiB) University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/45.4_ts.493"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(86)90122-8"},{"key":"e_1_2_10_4_1","unstructured":"Bonilla M. C. A.(2022).Sobreexpresi\u00f3n de genes en Streptomyces leeuwenhoekii C34 para aumentar la producci\u00f3n de agentes terap\u00e9uticos[Universidad de Chile].https:\/\/doi.org\/10.58011\/atjd-1b76."},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-142-3-649"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10482-014-0139-y"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-011-3304-5"},{"key":"e_1_2_10_8_1","unstructured":"Castro J. 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