{"entity": "publication", "iuid": "91d81459e6f04267a733a215a5473c19", "timestamp": "2026-09-08T10:05:23.858Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/91d81459e6f04267a733a215a5473c19.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/91d81459e6f04267a733a215a5473c19"}}, "title": "Improved production of Taxol\u00ae precursors in S. cerevisiae using combinatorial in silico design and metabolic engineering.", "authors": [{"family": "Malc\u0131", "given": "Koray", "initials": "K"}, {"family": "Santib\u00e1\u00f1ez", "given": "Rodrigo", "initials": "R"}, {"family": "Jonguitud-Borrego", "given": "Nestor", "initials": "N"}, {"family": "Santoyo-Garcia", "given": "Jorge H", "initials": "JH"}, {"family": "Kerkhoven", "given": "Eduard J", "initials": "EJ"}, {"family": "Rios-Solis", "given": "Leonardo", "initials": "L"}], "type": "journal article", "published": "2023-11-29", "journal": {"title": "Microb Cell Fact", "issn": "1475-2859", "volume": "22", "issue": "1", "pages": "243", "issn-l": "1475-2859"}, "abstract": "Integrated metabolic engineering approaches that combine system and synthetic biology tools enable the efficient design of microbial cell factories for synthesizing high-value products. In this study, we utilized in silico design algorithms on the yeast genome-scale model to predict genomic modifications that could enhance the production of early-step Taxol\u00ae in engineered Saccharomyces cerevisiae cells.\n\nUsing constraint-based reconstruction and analysis (COBRA) methods, we narrowed down the solution set of genomic modification candidates. We screened 17 genomic modifications, including nine gene deletions and eight gene overexpressions, through wet-lab studies to determine their impact on taxadiene production, the first metabolite in the Taxol\u00ae biosynthetic pathway. Under different cultivation conditions, most single genomic modifications resulted in increased taxadiene production. The strain named KM32, which contained four overexpressed genes (ILV2, TRR1, ADE13, and ECM31) involved in branched-chain amino acid biosynthesis, the thioredoxin system, de novo purine synthesis, and the pantothenate pathway, respectively, exhibited the best performance. KM32 achieved a 50% increase in taxadiene production, reaching 215 mg/L. Furthermore, KM32 produced the highest reported yields of taxa-4(20),11-dien-5\u03b1-ol (T5\u03b1-ol) at 43.65 mg/L and taxa-4(20),11-dien-5-\u03b1-yl acetate (T5\u03b1Ac) at 26.2 mg/L among early-step Taxol\u00ae metabolites in S. cerevisiae.\n\nThis study highlights the effectiveness of computational and integrated approaches in identifying promising genomic modifications that can enhance the performance of yeast cell factories. By employing in silico design algorithms and wet-lab screening, we successfully improved taxadiene production in engineered S. cerevisiae strains. The best-performing strain, KM32, achieved substantial increases in taxadiene as well as production of T5\u03b1-ol and T5\u03b1Ac. These findings emphasize the importance of using systematic and integrated strategies to develop efficient yeast cell factories, providing potential implications for the industrial production of high-value isoprenoids like Taxol\u00ae.", "doi": "10.1186/s12934-023-02251-7", "pmid": "38031061", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10687855"}, {"db": "pii", "key": "10.1186/s12934-023-02251-7"}], "notes": [], "created": "2026-08-21T12:39:18.230Z", "modified": "2026-08-21T12:39:18.244Z"}