CELL FACTORIES FOR IMPROVED PRODUCTION OF COMPOUNDS AND PROTEINS DEPENDENT ON IRON SULFUR CLUSTERS
申请人:Biosyntia ApS
公开号:EP3683227A1
公开(公告)日:2020-07-22
The invention relates to a genetically modified prokaryotic cell capable of improved iron-sulfur cluster delivery, characterized by a modified gene encoding a mutant Iron Sulfur Cluster Regulator (IscR) as well as one or more transgenes or upregulated endogenous genes encoding iron-sulfur (Fe-S) cluster polypeptides or proteins that catalyze complex radical-mediated molecular rearrangements, electron transfer, radical or non-redox reactions, sulfur donation or perform regulatory functions. Prokaryotic cells of the invention are characterized by enhanced activity of these iron-sulfur (Fe-S) cluster polypeptides, thereby enhancing their respective functional capacity, as well as facilitating enhanced yields of diverse compounds in free and protein-bound forms, including heme, hemoproteins, tetrapyrroles, B vitamins, amino acids, δ-aminolevulinic acid, biofuels, isoprenoids, pyrroloquinoline quinone, ammonia, indigo or their precursors, whose biosynthesis depends on their activity. The invention further relates to a method for producing each of said compounds, or their precursors using the genetically modified prokaryotic cell of the invention; as well as the use of the genetically modified prokaryotic cell.
本发明涉及一种能够改善铁硫簇传递的转基因原核细胞,其特征是具有编码突变型铁硫簇调节器(IscR)的修饰基因以及一个或多个编码铁硫(Fe-S)簇多肽或蛋白质的转基因或上调内源基因,这些基因或蛋白质可催化复杂的自由基介导的分子重排、电子转移、自由基或非氧化还原反应、硫捐赠或执行调节功能。本发明原核细胞的特点是这些铁硫(Fe-S)簇多肽的活性增强,从而提高了它们各自的功能能力,并促进了游离和蛋白结合形式的多种化合物产量的提高、这些化合物包括血红素、血蛋白、四吡咯、B 族维生素、氨基酸、δ-氨基乙酰丙酸、生物燃料、异戊二烯、吡咯喹啉醌、氨、靛蓝或其前体,其生物合成取决于它们的活性。本发明还涉及使用本发明的转基因原核细胞生产上述每种化合物或其前体的方法;以及转基因原核细胞的使用。