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通过工程手段在[具体对象]中构建甲羟戊酸途径以生产番茄红素。

Engineering a mevalonate pathway in for the production of lycopene.

作者信息

Su Qixuan, Cheng Ping, Sun Jiyuan, Zhang Yulin, Zheng Yang, Jiang Xiao-Ran, Rao Xiancai

机构信息

Cancer Center, Medical Research Institute, Southwest University, Chongqing, China.

Department of Microbiology, College of Basic Medical Sciences, Army Medical University (Third Military Medical University), Chongqing, China.

出版信息

Front Microbiol. 2023 Jan 16;13:1100745. doi: 10.3389/fmicb.2022.1100745. eCollection 2022.

Abstract

INTRODUCTION

Red-colored lycopene has received remarkable attention in medicine because of its antioxidant properties for reducing the risks of many human cancers. However, the extraction of lycopene from natural hosts is limited. Moreover, the chemically synthesized lycopene raises safety concerns due to residual chemical reagents. is a versatile chassis for the production of fine chemicals because of its open growth property without sterilization.

METHODS

A heterologous mevalonate (MVA) pathway was introduced into strain TD1.0 to engineer a bacterial host for lycopene production. A pTer7 plasmid mediating the expression of six MVA pathway genes under the control of a phage and an promoters and a pTer3 plasmid providing lycopene biosynthesis downstream genes derived from were constructed and transformed into TD1.0. The production of lycopene in the engineered was evaluated. Optimization of engineered bacteria was performed to increase lycopene yield.

RESULTS

The engineered TD1.0/pTer7-pTer3 produced lycopene at a maximum yield of 0.20 mg/g dried cell weight (DCW). Replacing downstream genes with those from elevated the lycopene production to 0.70 mg/g DCW in the TD1.0/pTer7-pTer5 strain. Optimizing the promoter in plasmid pTer7 with a relatively weak even increased the lycopene production to 1.22 mg/g DCW. However, the change in the promoter in pTer7 with did not improve the yield of lycopene.

CONCLUSION

We first engineered an for the lycopene production. The co-optimization of downstream genes and promoters governing MVA pathway gene expressions can synergistically enhance the microbial overproduction of lycopene.

摘要

引言

红色的番茄红素因其抗氧化特性可降低多种人类癌症风险而在医学领域备受关注。然而,从天然宿主中提取番茄红素存在局限性。此外,化学合成的番茄红素因残留化学试剂而引发安全问题。由于其无需灭菌即可开放生长的特性,[具体微生物名称未给出]是生产精细化学品的通用底盘。

方法

将异源甲羟戊酸(MVA)途径引入[具体微生物名称未给出]菌株TD1.0,构建用于生产番茄红素的细菌宿主。构建了一个pTer7质粒,其在噬菌体[具体名称未给出]和[具体名称未给出]启动子控制下介导六个MVA途径基因的表达,以及一个pTer3质粒,其提供源自[具体微生物名称未给出]的番茄红素生物合成下游基因,并将其转化到TD1.0中。评估了工程化[具体微生物名称未给出]中番茄红素的产量。对工程菌进行优化以提高番茄红素产量。

结果

工程化的TD1.0/pTer7-pTer3产生番茄红素的最大产量为0.20毫克/克干细胞重量(DCW)。用来自[具体微生物名称未给出]的下游基因替换后,TD1.0/pTer7-pTer5菌株中的番茄红素产量提高到0.70毫克/克DCW。用相对较弱的[具体名称未给出]优化质粒pTer7中的[具体启动子名称未给出]启动子,甚至使番茄红素产量提高到1.22毫克/克DCW。然而,用[具体名称未给出]改变pTer7中的[具体启动子名称未给出]启动子并没有提高番茄红素产量。

结论

我们首次构建了用于生产番茄红素的[具体微生物名称未给出]。对控制MVA途径基因表达的下游基因和启动子进行共同优化可协同增强微生物对番茄红素的过量生产。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1096/9885113/f39d87f065e7/fmicb-13-1100745-g001.jpg

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