文献类型：期刊文献

中文题名：Synergistic increase in coproporphyrinⅢbiosynthesis by mitochondrial compartmentalization in engineered Saccharomyces cerevisiae

作者：Qidi Guo[1];Jiaqi Xu[1,3];Jiacun Li[1];Shuyan Tang[1];Yuhui Cheng[1];Bei Gao[1];Liang-Bin Xiong[3];Jie Xiong[2];Feng-Qing Wang[1];Dong-Zhi Wei[1]

机构：[1]State Key Lab of Bioreactor Engineering,Newworld Institute of Biotechnology,East China University of Science and Technology,Shanghai,200237,China;[2]Department of Gastroenterology,Tongji Institute of Digestive Disease,Tongji Hospital,School of Medicine,TongJi University,Shanghai,200065,China;[3]Shanghai Key Laboratory of Molecular Imaging,School of Pharmacy,Shanghai University of Medicine and Health Sciences,Shanghai,201318,China

年份：2024

卷号：9

期号：4

起止页码：834

中文期刊名：Synthetic and Systems Biotechnology

外文期刊名：合成和系统生物技术(英文)

收录：CSCD:【CSCD2023_2024】；

基金：supported by the grant from the National Key Research and Development Program of China(2021YFC2100300);2023 Double World-class Project Key Program“Intelligent Biomanufacturing”.

语种：英文

中文关键词：CoproporphyrinⅢ;Saccharomyces cerevisiae;Mitochondrial compartmentalization;Anti-oxidation

摘要：CoproporphyrinⅢ(CPⅢ),a natural porphyrin derivative,has extensive applications in the biomedical and material industries.S.cerevisiae has previously been engineered to highly accumulate the CPⅢprecursor 5-aminolevulinic acid(ALA)through the C4 pathway.In this study,a combination of cytoplasmic metabolic engineering and mitochondrial compartmentalization was used to enhance CPⅢproduction in S.cerevisiae.By integrating pathway genes into the chromosome,the CPⅢtiter gradually increased to 32.5±0.5 mg/L in shake flask cultivation.Nevertheless,increasing the copy number of pathway genes did not consistently enhance CPⅢsynthesis.Hence,the partial synthesis pathway was compartmentalized in mitochondria to evaluate its effectiveness in increasing CPⅢproduction.Subsequently,by superimposing the mitochondrial compartmentalization strategy on cytoplasmic metabolic engineered strains,the CPⅢtiter was increased to 64.3±1.9 mg/L.Furthermore,augmenting antioxidant pathway genes to reduce reactive oxygen species(ROS)levels effectively improved the growth of engineered strains,resulting in a further increase in the CPⅢtiter to 82.9±1.4 mg/L.Fed-batch fermentations in a 5 L bioreactor achieved a titer of 402.8±9.3 mg/L for CPⅢ.This study provides a new perspective on engineered yeast for the microbial production of porphyrins.