文章基本信息

标题：Optimization of the heme biosynthesis pathway for the production of 5-aminolevulinic acid in Escherichia coli
本地全文：下载
作者：Junli Zhang ; Zhen Kang ; Jian Chen 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：5
期号：1
DOI：10.1038/srep08584
语种：English
出版社：Springer Nature
摘要：5-Aminolevulinic acid (ALA), the committed intermediate of the heme biosynthesis pathway, shows significant promise for cancer treatment. Here, we identified that in addition to hemA and hemL , hemB , hemD , hemF , hemG and hemH are also the major regulatory targets of the heme biosynthesis pathway. Interestingly, up-regulation of hemD and hemF benefited ALA accumulation whereas overexpression of hemB , hemG and hemH diminished ALA accumulation. Accordingly, by combinatorial overexpression of the hemA , hemL , hemD and hemF with different copy-number plasmids, the titer of ALA was improved to 3.25 g l⁻¹. Furthermore, in combination with transcriptional and enzymatic analysis, we demonstrated that ALA dehydratase (HemB) encoded by hemB is feedback inhibited by the downstream intermediate protoporphyrinogen IX. This work has great potential to be scaled-up for microbial production of ALA and provides new important insights into the regulatory mechanism of the heme biosynthesis pathway.