Thermodynamics contributes to high limonene productivity in cyanobacteria

IF 3.7 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Metabolic Engineering Communications Pub Date : 2022-06-01 DOI:10.1016/j.mec.2022.e00193
Shrameeta Shinde , Sonali Singapuri , Zhenxiong Jiang , Bin Long , Danielle Wilcox , Camille Klatt , J. Andrew Jones , Joshua S. Yuan , Xin Wang
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引用次数: 7

Abstract

Terpenoids are a large group of secondary metabolites with broad industrial applications. Engineering cyanobacteria is an attractive route for the sustainable production of commodity terpenoids. Currently, a major obstacle lies in the low productivity attained in engineered cyanobacterial strains. Traditional metabolic engineering to improve pathway kinetics has led to limited success in enhancing terpenoid productivity. In this study, we reveal thermodynamics as the main determinant for high limonene productivity in cyanobacteria. Through overexpressing the primary sigma factor, a higher photosynthetic rate was achieved in an engineered strain of Synechococcus elongatus PCC 7942. Computational modeling and wet lab analyses showed an increased flux toward both native carbon sink glycogen synthesis and the non-native limonene synthesis from photosynthate output. On the other hand, comparative proteomics showed decreased expression of terpene pathway enzymes, revealing their limited role in determining terpene flux. Lastly, growth optimization by enhancing photosynthesis has led to a limonene titer of 19 mg/L in 7 days with a maximum productivity of 4.3 mg/L/day. This study highlights the importance of enhancing photosynthesis and substrate input for the high productivity of secondary metabolic pathways, providing a new strategy for future terpenoid engineering in phototrophs.

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热力学有助于蓝藻的高柠檬烯生产率
萜类化合物是一类具有广泛工业应用的次生代谢物。工程蓝藻是可持续生产商品萜类化合物的一条有吸引力的途径。目前,一个主要的障碍在于低生产力达到工程蓝藻菌株。传统的代谢工程,以改善途径动力学导致有限的成功,在提高萜类化合物的生产力。在这项研究中,我们揭示了热力学作为蓝藻中高柠檬烯生产力的主要决定因素。通过过表达初级sigma因子,长聚球菌工程菌株PCC 7942获得了较高的光合速率。计算模型和湿实验室分析表明,天然碳汇糖原合成和光合产物输出的非天然柠檬烯合成的通量都增加了。另一方面,比较蛋白质组学显示萜烯途径酶的表达减少,揭示了它们在决定萜烯通量方面的作用有限。最后,通过加强光合作用进行生长优化,使柠檬烯在7天内滴度达到19 mg/L,最大产量为4.3 mg/L/d。该研究强调了加强光合作用和底物输入对于提高次生代谢途径的生产力的重要性,为未来光养生物萜类工程提供了新的策略。
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来源期刊
Metabolic Engineering Communications
Metabolic Engineering Communications Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
13.30
自引率
1.90%
发文量
22
审稿时长
18 weeks
期刊介绍: Metabolic Engineering Communications, a companion title to Metabolic Engineering (MBE), is devoted to publishing original research in the areas of metabolic engineering, synthetic biology, computational biology and systems biology for problems related to metabolism and the engineering of metabolism for the production of fuels, chemicals, and pharmaceuticals. The journal will carry articles on the design, construction, and analysis of biological systems ranging from pathway components to biological complexes and genomes (including genomic, analytical and bioinformatics methods) in suitable host cells to allow them to produce novel compounds of industrial and medical interest. Demonstrations of regulatory designs and synthetic circuits that alter the performance of biochemical pathways and cellular processes will also be presented. Metabolic Engineering Communications complements MBE by publishing articles that are either shorter than those published in the full journal, or which describe key elements of larger metabolic engineering efforts.
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