{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T15:03:26Z","timestamp":1790348606247,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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                    Lactonic sophorolipids (LSLs) are high\u2010value glycolipid biosurfactants with superior bioactivities, yet their industrial application is hampered by the low lactonization efficiency of wild\u2010type strains. In this study, we employed a transcriptomics\u2010driven approach to decode the regulatory landscape of the underexplored yeast\n                    <jats:italic>Starmerella riodocensis<\/jats:italic>\n                    GT\u2010SL1R and engineer it for high\u2010titer LSL production. Comparative transcriptome analysis under nitrogen limitation revealed a massive metabolic reprogramming, identifying 497 upregulated genes, including the core SL biosynthetic cluster (\n                    <jats:italic>CYP52M1<\/jats:italic>\n                    ,\n                    <jats:italic>ugta1<\/jats:italic>\n                    ,\n                    <jats:italic>ugtb1<\/jats:italic>\n                    ,\n                    <jats:italic>at<\/jats:italic>\n                    , and\n                    <jats:italic>mdr1<\/jats:italic>\n                    ). Crucially, we identified a novel lactone esterase (\n                    <jats:italic>Sr<\/jats:italic>\n                    LE) with only 49% similarity to the well\u2010known\n                    <jats:italic>Sb<\/jats:italic>\n                    LE from\n                    <jats:italic>Starmrella bombicola<\/jats:italic>\n                    . While growth\u2010related pathways (ribosome biogenesis and DNA replication) were repressed, nitrogen recycling mechanisms were activated to fuel SL biosynthesis. Directed metabolic engineering of the lactonization pathway through\n                    <jats:italic>SrLE<\/jats:italic>\n                    or\n                    <jats:italic>SbLE<\/jats:italic>\n                    overexpression, coupled with fed\u2010batch fermentation in a 5\u2010L bioreactor, achieved exceptional LSL titers of 189.33\u2009g\u00b7L\n                    <jats:sup>\u22121<\/jats:sup>\n                    and 191.45\u2009g\u00b7L\n                    <jats:sup>\u22121<\/jats:sup>\n                    , respectively. Conversely,\n                    <jats:italic>SrLE<\/jats:italic>\n                    knockout resulted in the exclusive production of acidic SLs, confirming its pivotal role in lactonization. These results provide deep mechanistic insights into SL biosynthesis and demonstrate the power of targeted enzyme engineering in creating robust microbial cell factories for specialized glycolipid production.\n                  <\/jats:p>","DOI":"10.1002\/bit.70381","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:37:07Z","timestamp":1790347027000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomics\u2010Driven Identification and Engineering of a Novel Lactone Esterase (\n                    <i>Sr<\/i>\n                    LE) for Efficient Sophorolipid Lactonization in the Yeast\n                    <i>Starmerella riodocensis<\/i>"],"prefix":"10.1002","author":[{"given":"Sirawich","family":"Sapsirisuk","sequence":"first","affiliation":[{"name":"Excellent Research Laboratory for Yeast Innovation, Biochemical Technology Division, School of Bioresources &amp; Technology King Mongkut's University of Technology Thonburi (KMUTT) Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6072-4629","authenticated-orcid":false,"given":"Jungho","family":"Lee","sequence":"additional","affiliation":[{"name":"BioPort Group, Centre for Synthetic Biology, Department of Biotechnology Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8144-6466","authenticated-orcid":false,"given":"Inge No\u00eblle Adrienne Van","family":"Bogaert","sequence":"additional","affiliation":[{"name":"BioPort Group, Centre for Synthetic Biology, Department of Biotechnology Ghent University Ghent Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4143-4780","authenticated-orcid":false,"given":"Nitnipa","family":"Soontorngun","sequence":"additional","affiliation":[{"name":"Excellent Research Laboratory for Yeast Innovation, Biochemical Technology Division, School of Bioresources &amp; Technology King Mongkut's University of Technology Thonburi (KMUTT) Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s12934-022-01852-y","article-title":"Production of New Antimicrobial Palm Oil\u2010Derived Sophorolipids by the Yeast Starmerella riodocensis sp. Nov. Against Candida Albicans Hyphal and Biofilm Formation","volume":"21","author":"Alfian A. R.","year":"2022","journal-title":"Microbial Cell Factories"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"issue":"9","key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s11746-005-1120-3","article-title":"Sophorolipid Biosynthesis From a Biodiesel Co\u2010Product Stream","volume":"82","author":"Ashby R. D.","year":"2005","journal-title":"Journal of the American Oil Chemists' Society"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-010-2589-0"},{"issue":"6","key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.plipres.2009.08.005","article-title":"Yarrowia Lipolytica as a Model for Bio\u2010Oil Production","volume":"48","author":"Beopoulos A.","year":"2009","journal-title":"Progress in lipid research"},{"issue":"6","key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1016\/j.biochi.2009.02.004","article-title":"Yarrowia Lipolytica: A Model and a Tool to Understand the Mechanisms Implicated in Lipid Accumulation","volume":"91","author":"Beopoulos A.","year":"2009","journal-title":"Biochimie"},{"issue":"3","key":"e_1_2_9_8_1","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms8030453","article-title":"Lipid Production From Sugarcane Top Hydrolysate and Crude Glycerol With Rhodosporidiobolus Fluvialis Using a Two\u2010Stage Batch\u2010Cultivation Strategy With Separate Optimization of Each Stage","volume":"8","author":"Boonyarit J.","year":"2020","journal-title":"Microorganisms"},{"issue":"1","key":"e_1_2_9_9_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1111\/j.1574-6976.2002.tb00599.x","article-title":"Microbial Carboxyl Esterases: Classification, Properties and Application in Biocatalysis","volume":"26","author":"Bornscheuer U. T.","year":"2002","journal-title":"FEMS microbiology reviews"},{"issue":"17","key":"e_1_2_9_10_1","doi-asserted-by":"crossref","DOI":"10.3390\/molecules27175556","article-title":"Sophorolipids\u2014Bio\u2010Based Antimicrobial Formulating Agents for Applications in Food and Health","volume":"27","author":"Cho W. Y.","year":"2022","journal-title":"Molecules"},{"issue":"22","key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"9529","DOI":"10.1007\/s00253-016-7633-2","article-title":"Characterization of a Novel Enzyme\u2014Starmerella Bombicola Lactone Esterase (SBLE)\u2014Responsible for Sophorolipid Lactonization","volume":"100","author":"Ciesielska K.","year":"2016","journal-title":"Applied Microbiology and Biotechnology"},{"key":"e_1_2_9_12_1","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.jprot.2013.12.026","article-title":"Exoproteome Analysis of Starmerella Bombicola Results in the Discovery of an Esterase Required for Lactonization of Sophorolipids","volume":"98","author":"Ciesielska K.","year":"2014","journal-title":"Journal of proteomics"},{"issue":"13","key":"e_1_2_9_13_1","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1002\/1873-3468.13469","article-title":"Protein\u2010Facilitated Transport of Hydrophobic Molecules Across the Yeast Plasma Membrane","volume":"593","author":"Claus S.","year":"2019","journal-title":"Febs Letters"},{"issue":"6","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.nbt.2015.02.009","article-title":"Sophorolipid Biosurfactants: Possible Uses as Antibacterial and Antibiofilm Agent","volume":"32","author":"De Rienzo M. A. D.","year":"2015","journal-title":"New biotechnology"},{"issue":"4","key":"e_1_2_9_15_1","doi-asserted-by":"crossref","DOI":"10.3390\/colloids2040042","article-title":"Increasing Uniformity of Biosurfactant Production in Starmerella bombicola via the Expression of Chimeric Cytochrome P450s","volume":"2","author":"Geys R.","year":"2018","journal-title":"Colloids and Interfaces"},{"issue":"4","key":"e_1_2_9_16_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/yea.320110408","article-title":"Studies on the Transformation of Intact Yeast Cells by the LiAc\/SS\u2010DNA\/PEG Procedure","volume":"11","author":"Gietz R. D.","year":"1995","journal-title":"Yeast"},{"issue":"4","key":"e_1_2_9_17_1","doi-asserted-by":"crossref","first-page":"397","DOI":"10.15252\/embj.201696010","article-title":"Nutrient Sensing and TOR Signaling in Yeast and Mammals","volume":"36","author":"Gonz\u00e1lez A.","year":"2017","journal-title":"The EMBO journal"},{"key":"e_1_2_9_18_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.indcrop.2022.116091","article-title":"Enhanced Palm Oil\u2010Derived Sophorolipid Production From Yeast to Generate Biodegradable Plastic Precursors","volume":"192","author":"Intasit R.","year":"2023","journal-title":"Industrial Crops and Products"},{"key":"e_1_2_9_19_1","first-page":"601","article-title":"Biosynthesis of Glycolipids and Their Genetic Engineering","volume":"19","author":"Jezierska S.","year":"2019","journal-title":"Microbial Biosurfactants and their Environmental and Industrial Applications"},{"issue":"21","key":"e_1_2_9_20_1","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal W and Clustal X Version 2.0","volume":"23","author":"Larkin M. A.","year":"2007","journal-title":"Bioinformatics"},{"key":"e_1_2_9_21_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biortech.2025.133524","article-title":"Unlocking Chain Length Elongation to Expand the Long\u2010Chain Dicarboxylic Acid Repertoire in Starmerella Bombicola","volume":"440","author":"Lee J.","year":"2025","journal-title":"Bioresource Technology"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa937"},{"issue":"1","key":"e_1_2_9_23_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s11427-017-9304-8","article-title":"Rational Design for Fungal Laccase Production in the Model Host Aspergillus Nidulans","volume":"62","author":"Li W.","year":"2019","journal-title":"Science China Life Sciences"},{"issue":"8","key":"e_1_2_9_24_1","doi-asserted-by":"crossref","DOI":"10.3390\/microorganisms7080247","article-title":"Taxonomic Distribution of Cytochrome P450 Monooxygenases (CYPs) Among the Budding Yeasts (Sub\u2010Phylum Saccharomycotina)","volume":"7","author":"Linder T.","year":"2019","journal-title":"Microorganisms"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2012.07.003"},{"issue":"8","key":"e_1_2_9_26_1","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1002\/ejlt.201100014","article-title":"Lipids of Oleaginous Yeasts. Part I: Biochemistry of Single Cell Oil Production","volume":"113","author":"Papanikolaou S.","year":"2011","journal-title":"European Journal of Lipid Science and Technology"},{"key":"e_1_2_9_27_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.biombioe.2020.105597","article-title":"Economical Lipid Production From Crude Glycerol Using Rhodosporidiobolus fluvialis DMKU\u2010RK253 in a Two\u2010Stage Cultivation under Non\u2010Sterile Conditions","volume":"138","author":"Polburee P.","year":"2020","journal-title":"Biomass and Bioenergy"},{"issue":"7","key":"e_1_2_9_28_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0006441","article-title":"Circular Polymerase Extension Cloning of Complex Gene Libraries and Pathways","volume":"4","author":"Quan J.","year":"2009","journal-title":"PloS one"},{"issue":"5","key":"e_1_2_9_29_1","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1007\/s00253-012-4437-x","article-title":"Sophorolipids: Improvement of the Selective Production by Starmerella Bombicola Through the Design of Nutritional Requirements","volume":"97","author":"Ribeiro I. A.","year":"2013","journal-title":"Applied microbiology and biotechnology"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25815"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.24895"},{"issue":"12","key":"e_1_2_9_32_1","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.1002\/bit.23248","article-title":"One\u2010Step Production of Unacetylated Sophorolipids by An Acetyltransferase Negative Candida Bombicola","volume":"108","author":"Saerens K. M.","year":"2011","journal-title":"Biotechnology and Bioengineering"},{"issue":"4","key":"e_1_2_9_33_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1002\/yea.1838","article-title":"Cloning and Functional Characterization of the Udp\u2010Glucosyltransferase UgtB1 Involved in Sophorolipid Production by Candida Bombicola and Creation of a Glucolipid\u2010Producing Yeast Strain","volume":"28","author":"Saerens K. M.","year":"2011","journal-title":"Yeast"},{"issue":"10","key":"e_1_2_9_34_1","doi-asserted-by":"crossref","DOI":"10.3390\/jof8101100","article-title":"Discovery of Oleaginous Yeast From Mountain Forest Soil in Thailand","volume":"8","author":"Sapsirisuk S.","year":"2022","journal-title":"Journal of Fungi"},{"key":"e_1_2_9_35_1","doi-asserted-by":"crossref","DOI":"10.1093\/femsyr\/foag007","article-title":"Optimising Carbon\u2010to\u2010Nitrogen Ratios for Enhanced Antimicrobial Sophorolipid Production in Starmerella Riodocensis Gt\u2010Sl1r","volume":"26","author":"Sapsirisuk S.","year":"2026","journal-title":"FEMS Yeast Research"},{"key":"e_1_2_9_36_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymben.2012.08.007","article-title":"Engineering the Push and Pull of Lipid Biosynthesis in Oleaginous Yeast Yarrowia Lipolytica for Biofuel Production","volume":"15","author":"Tai M.","year":"2013","journal-title":"Metabolic engineering"},{"key":"e_1_2_9_37_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.indcrop.2024.118089","article-title":"Enhanced Production of Yeast Biosurfactant Sophorolipids Using Yeast Extract or the Alternative Nitrogen Source Soybean Meal","volume":"210","author":"Taowkrue E.","year":"2024","journal-title":"Industrial Crops and Products"},{"issue":"7","key":"e_1_2_9_38_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1038\/s41587-021-01156-3","article-title":"Signalp 6.0 Predicts All Five Types of Signal Peptides Using Protein Language Models","volume":"40","author":"Teufel F.","year":"2022","journal-title":"Nature biotechnology"},{"issue":"2","key":"e_1_2_9_39_1","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1742-4658.2010.07949.x","article-title":"The Role of Cytochrome P450 Monooxygenases in Microbial Fatty Acid Metabolism","volume":"278","author":"Van Bogaert I. N.","year":"2011","journal-title":"The FEBS journal"},{"issue":"3","key":"e_1_2_9_40_1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/mmi.12200","article-title":"The Biosynthetic Gene Cluster for Sophorolipids: A Biotechnological Interesting Biosurfactant Produced by S Tarmerella Bombicola","volume":"88","author":"Van Bogaert I. N.","year":"2013","journal-title":"Molecular microbiology"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10295-008-0386-x"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-007-0988-7"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2011.01.010"},{"issue":"1","key":"e_1_2_9_44_1","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-025-08816-3","article-title":"Yeast\u2010Derived Glycolipids Disrupt Candida Biofilm and Inhibit Expression of Genes in Cell Adhesion","volume":"15","author":"Watchaputi K.","year":"2025","journal-title":"Scientific Reports"},{"issue":"8","key":"e_1_2_9_45_1","doi-asserted-by":"crossref","first-page":"1724","DOI":"10.3390\/microorganisms9081724","article-title":"Two\u2010Stage Fermentation of Lipomyces Starkeyi for Production of Microbial Lipids and Biodiesel","volume":"9","author":"Zhang L.","year":"2021","journal-title":"Microorganisms"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.70381","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bit.70381","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.70381","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:37:12Z","timestamp":1790347032000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.70381"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":44,"alternative-id":["10.1002\/bit.70381"],"URL":"https:\/\/doi.org\/10.1002\/bit.70381","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]},"assertion":[{"value":"2026-06-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"bit.70381"}}