期刊
ACS SYNTHETIC BIOLOGY
卷 10, 期 2, 页码 286-296出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.0c00391
关键词
trihydroxycinnamoyl spermidines; phenolamides; yeast engineering; N-hydroxycinnamoyltransferase; precursor-directed biosynthesis; 4-coumarate-CoA ligase
资金
- ARD2020 Biopharmaceutical program of the Region Centre Val de Loire (BioPROPHARM project)
- ARD2020 Biopharmaceutical program of the Region Centre Val de Loire (CatharSIS project)
- ARD2020 Biopharmaceutical program of the Region Centre Val de Loire (ETOPOCentre project)
THCSpd are plant specialized metabolites with promising pharmacological activities, and can be biosynthesized in yeast using a dual enzymatic system. By exploring enzyme diversity and substrate promiscuities, various new-to-nature THCSpd can be produced, demonstrating a versatile biotechnological platform for tailor-made synthesis.
Trihydroxycinnamoyl spermidines (THCSpd) are plant specialized metabolites with promising pharmacological activities as antifungals, antibacterial, antiviral, and antidepressant drugs. However, their characterization and potential pharmaceutical exploitation are greatly impaired by the sourcing of these compounds, restricted to the pollen of core Eudicot plant species. In this work, we developed a precursor-directed biosynthesis of THCSpd in yeast using a dual enzymatic system based on 4-coumarate-CoA ligases (4CL) and spermidine N-hydroxycinnamoyltransferases (SHT). The system relies on the yeast endogenous spermidine pool and only requires hydroxycinnamic acids as exogenous precursors. By exploring 4CL isoforms and SHT diversity among plants, we have driven the production of 8 natural THCSpd, using single or mixed hydroxycinnamic acid precursors. Substrate promiscuities of 4CL and SHT were genuinely exploited to produce 8 new-to-nature THCSpd from exotic hydroxycinnamic and dihydrohydroxycinnamic acids, together with 3 new-to-nature THCSpd containing halogenated hydroxycinnamoyl moieties. In this work, we established a versatile and modular biotechnological production platform allowing the tailor-made THCSpd synthesis, constituting pioneer metabolic engineering for access to these valuable natural products.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据