Enhanced limonene production in a fast-growing cyanobacterium through combinatorial metabolic engineering.
Enhanced limonene production in a fast-growing cyanobacterium through combinatorial metabolic engineering.
复制标题
DOI：
10.1016/j.mec.2021.e00164
复制
发表时间：
2021-06
影响因子：
5.2
通讯作者：
Pakrasi HB
中科院分区：
文献类型：
--
作者：
Lin PC;Zhang F;Pakrasi HB
萜类化合物是一组庞大而多样化的具有商业应用的天然产品。微生物生产萜烯被认为是稳定供应这些复杂碳氢化合物的可行途径。蓝细菌，光合原核生物，是可持续生物生产的有吸引力的宿主，因为这些自养生物只需要光和CO2的生长。尽管蓝细菌已经被工程化以产生多种化合物，但它们的萜烯生产率通常较低。需要进一步的研究来确定提高蓝藻中萜烯产量的瓶颈反应。在这项研究中，我们设计了快速生长的蓝细菌细长聚球藻UTEX 2973，以生产商业使用的萜类化合物，柠檬烯。我们在编码香叶基香叶基焦磷酸合酶crtE的基因中发现了一个有益的突变，导致柠檬烯产量增加2.5倍。该工程菌株以8.2 mg L−1 day−1的速率产生16.4 mg L−1的柠檬烯，这比先前报道的其他蓝藻物种的柠檬烯生产率高8倍。此外，我们采用了组合代谢工程的方法来优化柠檬烯生物合成的上游途径中涉及的基因。通过调节编码MEP途径中的酶和香叶基焦磷酸合酶的基因的表达，我们表明表达水平的优化对于提高蓝细菌中柠檬烯的产量至关重要。用于柠檬烯生产的快速生长的蓝细菌细长聚球藻UTEX 2973的工程化。鉴定一种有益的突变，使柠檬烯产量增加2.5倍。柠檬烯生物合成途径的优化。
Terpenoids are a large and diverse group of natural products with commercial applications. Microbial production of terpenes is considered as a feasible approach for the stable supply of these complex hydrocarbons. Cyanobacteria, photosynthetic prokaryotes, are attractive hosts for sustainable bioproduction, because these autotrophs require only light and CO2 for growth. Despite cyanobacteria having been engineered to produce a variety of compounds, their productivities of terpenes are generally low. Further research is needed to determine the bottleneck reactions for enhancing terpene production in cyanobacteria. In this study, we engineered the fast-growing cyanobacterium Synechococcus elongatus UTEX 2973 to produce a commercially-used terpenoid, limonene. We identified a beneficial mutation in the gene encoding geranylgeranyl pyrophosphate synthase crtE, leading to a 2.5-fold increase in limonene production. The engineered strain produced 16.4 mg L−1 of limonene at a rate of 8.2 mg L−1 day−1, which is 8-fold higher than limonene productivities previously reported in other cyanobacterial species. Furthermore, we employed a combinatorial metabolic engineering approach to optimize genes involved in the upstream pathway of limonene biosynthesis. By modulating the expression of genes encoding the enzymes in the MEP pathway and the geranyl pyrophosphate synthase, we showed that optimization of the expression level is critical to enhance limonene production in cyanobacteria. Engineering of the fast growing cyanobacterium Synechococcus elongatus UTEX 2973 for limonene production. Identification of a beneficial mutation with 2.5-fold increase in limonene productivity. Pathway optimization for limonene biosynthesis.
登录
查看更多内容
影响因子：
4.6
作者：
Lin PC;Saha R;Zhang F;Pakrasi HB
通讯作者：
Pakrasi HB
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
DOI：
10.1073/pnas.1519220112
发表时间：
2015-12-01
影响因子：
11.1
作者：
Rubin, Benjamin E.;Wetmore, Kelly M.;Golden, Susan S.
通讯作者：
Golden, Susan S.
影响因子：
5.6
作者：
Feng, Yuchi;Morgan, R. Marc L.;Nixon, Peter J.
通讯作者：
Nixon, Peter J.
影响因子：
46.9
作者：
Salis, Howard M.;Mirsky, Ethan A.;Voigt, Christopher A.
通讯作者：
Voigt, Christopher A.