Metabolomic analysis reveals rewiring of <scp>S</scp>ynechocystis <scp>sp</scp>. <scp>PCC</scp> 6803 primary metabolism by ntcA overexpression

Osanai, Takashi; Oikawa, Akira; Iijima, Hiroko; Kuwahara, Ayuko; Asayama, Munehiko; Tanaka, Kan; Ikeuchi, Masahiko; Saito, Kazuki; Hirai, Masami Yokota

doi:10.1111/1462-2920.12554

Cited by 19 publications

(8 citation statements)

References 40 publications

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“…PCC 6803, which dramatically affected sugar, purine/pyrimidine nucleotide, organic acid and amino acid metabolisms. This study set an example to advance the understanding of metabolic regulation of unicellular cyanobacteria (Osanai et al, 2014 ). Dörries et al, investigated the impact of antibiotic compounds with different cellular targets on the metabolome of Staphylococcus aureus HG001.…”

Section: Discovery Metabolomicsmentioning

confidence: 99%

Functional metabolomics: from biomarker discovery to metabolome reprogramming

Peng¹,

Li²,

Peng³

2015

Protein Cell

268

200

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Metabolomics is emerging as a powerful tool for studying metabolic processes, identifying crucial biomarkers responsible for metabolic characteristics and revealing metabolic mechanisms, which construct the content of discovery metabolomics. The crucial biomarkers can be used to reprogram a metabolome, leading to an aimed metabolic strategy to cope with alteration of internal and external environments, naming reprogramming metabolomics here. The striking feature on the similarity of the basic metabolic pathways and components among vastly different species makes the reprogramming metabolomics possible when the engineered metabolites play biological roles in cellular activity as a substrate of enzymes and a regulator to other molecules including proteins. The reprogramming metabolomics approach can be used to clarify metabolic mechanisms of responding to changed internal and external environmental factors and to establish a framework to develop targeted tools for dealing with the changes such as controlling and/or preventing infection with pathogens and enhancing host immunity against pathogens. This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.

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Section: Discovery Metabolomicsmentioning

confidence: 99%

Functional metabolomics: from biomarker discovery to metabolome reprogramming

Peng¹,

Li²,

Peng³

2015

Protein Cell

268

200

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“…PCC 6803 [19, 22], a non-completely segregated mutant exhibited abolished activations of ntcA on positive regulons (e.g., glnA , glnB , and glnN promoters) [22] and repressions of ntcA on negative regulons (e.g., gifA and gifB promoters) [19]. On the other hand, overexpression of ntcA leads to wide alterations in primary metabolism and a close to 90% loss of the intracellular 2-OG pool [23]. In addition, NtcA directly acts on sugar catabolism, which is indispensable to metabolism in cyanobacteria, by activating the transcription of sigE [24] and rre37 [25].…”

Section: Introductionmentioning

confidence: 99%

Effects of global transcription factor NtcA on photosynthetic production of ethylene in recombinant Synechocystis sp. PCC 6803

Xie

Zhu

et al. 2017

Biotechnol Biofuels

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BackgroundCyanobacteria are considered potential photosynthetic microbial cell factories for biofuel and biochemical production. Ethylene, one of the most important organic chemicals, has been successfully synthesized in cyanobacteria by introducing an exogenous ethylene-forming enzyme (Efe). However, it remains challenging to significantly improve the biosynthetic efficiency of cyanobacterial ethylene. Genetic modification of transcription factors is a powerful strategy for reprogramming cellular metabolism toward target products. In cyanobacteria, nitrogen control A (NtcA), an important global transcription regulator of primary carbon/nitrogen metabolism, is expected to play a crucial role in ethylene biosynthesis.ResultsThe partial deletion of ntcA (MH021) enhanced ethylene production by 23%, while ntcA overexpression (MH023) in a single-copy efe recombinant Synechocystis (XX76) reduced ethylene production by 26%. Compared to XX76, the Efe protein content increased 1.5-fold in MH021. This result may be due to the release of the negative regulation of NtcA on promoter PcpcB, which controls efe expression. Glycogen content showed a 23% reduction in MH021, and the ratio of intracellular succinate to 2-oxoglutarate (2-OG) increased 4.8-fold. In a four-copy efe recombinant strain with partially deleted ntcA and a modified tricarboxylic acid (TCA) cycle (MH043), a peak specific ethylene production rate of 2463 ± 219 μL L−1 h−1 OD730−1 was achieved, which is higher than previously reported.ConclusionsThe effects of global transcription factor NtcA on ethylene synthesis in genetically engineered Synechocystis sp. PCC 6803 were evaluated, and the partial deletion of ntcA enhanced ethylene production in both single-copy and multi-copy efe recombinant Synechocystis strains. Increased Efe expression, accelerated TCA cycling, and redirected carbon flux from glycogen probably account for this improvement. The results show great potential for improving ethylene synthetic efficiency in cyanobacteria by modulating global regulation factors.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-017-0832-y) contains supplementary material, which is available to authorized users.

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“…Yet, our understanding of the acetyl-CoA metabolism in cyanobacteria is limited. A few studies, that have addressed the question how acetyl-CoA pools respond during nitrogen deprivation came to controversial results: in some studies, the acetyl-CoA pools increased (Joseph et al, 2014; Anfelt et al, 2015), or were almost unchanged (Schlebusch and Forchhammer, 2010) whereas other reported modest (Osanai et al, 2014) or strong decrease (Hondo et al, 2015) upon nitrogen deprivation. Different growth conditions, extraction procedures, or data normalization could account for the divergence.…”

Section: Introductionmentioning

confidence: 99%

Interaction of the Nitrogen Regulatory Protein GlnB (PII) with Biotin Carboxyl Carrier Protein (BCCP) Controls Acetyl-CoA Levels in the Cyanobacterium Synechocystis sp. PCC 6803

Hauf¹,

Schmid²,

Gerhardt³

et al. 2016

Front. Microbiol.

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The family of PII signal transduction proteins (members GlnB, GlnK, NifI) plays key roles in various cellular processes related to nitrogen metabolism at different functional levels. Recent studies implied that PII proteins may also be involved in the regulation of fatty acid metabolism, since GlnB proteins from Proteobacteria and from Arabidopsis thaliana were shown to interact with biotin carboxyl carrier protein (BCCP) of acetyl-CoA carboxylase (ACC). In case of Escherichia coli ACCase, this interaction reduces the kcat of acetyl-CoA carboxylation, which should have a marked impact on the acetyl-CoA metabolism. In this study we show that the PII protein of a unicellular cyanobacterium inhibits the biosynthetic activity of E. coli ACC and also interacts with cyanobacterial BCCP in an ATP and 2-oxoglutarate dependent manner. In a PII mutant strain of Synechocystis strain PCC 6803, the lacking control leads to reduced acetyl-CoA levels, slightly increased levels of fatty acids and formation of lipid bodies as well as an altered fatty acid composition.

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Metabolomic analysis reveals rewiring of Synechocystis sp. PCC 6803 primary metabolism by ntcA overexpression

Cited by 19 publications

References 40 publications

Functional metabolomics: from biomarker discovery to metabolome reprogramming

Functional metabolomics: from biomarker discovery to metabolome reprogramming

Effects of global transcription factor NtcA on photosynthetic production of ethylene in recombinant Synechocystis sp. PCC 6803

Interaction of the Nitrogen Regulatory Protein GlnB (PII) with Biotin Carboxyl Carrier Protein (BCCP) Controls Acetyl-CoA Levels in the Cyanobacterium Synechocystis sp. PCC 6803

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