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Functional metabolomics: from biomarker discovery to metabolome reprogramming.

Peng B, Li H, Peng XX - Protein Cell (2015)

Bottom Line: 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 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.This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.

View Article: PubMed Central - PubMed

Affiliation: Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Bacterial infection-sensitive metabolomeis reprogrammed to bacterial anti-infective metabolome by exogenous crucial metabolites. Sublethal dose of pathogen causes hosts either to die or survival, which is related to their metabolomes. Crucial metabolites can be identified by comparison of the two metabolomes. Exogenous addition of the crucial metabolites increases the chances of survival
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Fig2: Bacterial infection-sensitive metabolomeis reprogrammed to bacterial anti-infective metabolome by exogenous crucial metabolites. Sublethal dose of pathogen causes hosts either to die or survival, which is related to their metabolomes. Crucial metabolites can be identified by comparison of the two metabolomes. Exogenous addition of the crucial metabolites increases the chances of survival

Mentions: Besides the reprogramming metabolome of immune regulator such as IFN-α2b, the approach can be used to restore host defense ability from susceptibility to resistance to pathogens. Streptococcosis causes massive tilapia kills, which results in heavy economic losses of tilapia farming industry. Current antibiotic options are limited and possess severe practical limitations and potential adverse environmental impacts. GC-MS based metabolomics is used to characterize variation of metabolomes in response to S. iniae. Nine key metabolites that separate the survivals from the dying and control were identified. N-acetylglucosamine was the most critical metabolite elevated in survival groups but decreased in dying groups. The reversal change formed a characteristic feature as a result of tilapias against infection caused by S. iniae. When exogenous N-acetylglucosamine was added, the survival ability significantly elevated by at least 35%. In anti-S. agalactiae metabolome, significant decrease of several amino acids and their metabolic pathways was characterized. L-proline was identified as a crucial biomarker. Three-day L-proline-supplemented tilapias by intraperitoneal injection or oral administration before challenging with S. agalactiae showed the significant higher resistance against the challenging bacteria, elevating 60% survival rates in group with 2 mg L-proline injection (Cheng et al., 2014). In the same way, the approach can be used to reprogram a metabolic strategy to modulate the effect of temperature on bacterial toxicity. S. agalactiae killed more tilapias in higher than lower temperatures, where 50% mortality and 70% mortality were reported for tilapias cultured in 25°C and 30°C, respectively while no death was detected at 20°C (Zhao et al., 2015). We investigated the metabolome change in the livers of tilapia. Thirty-six and forty-five varied abundance of metabolites were identified in livers of tilapias cultured at 25°C and 30°C, respectively. Decreasing abundance of L-proline was identified as a crucial biomarker for indexing higher water temperature and a potential modulator to reduce the high death. This was validated by engineering injection or oral addition of L-proline. Exogenous L-proline led to elevated amino acid metabolism, which contributed to the elevated survivals (Zhao et al., 2015). These results highlight the way to identify drug potentials to combat microbial infections though reprogramming metabolome (Fig. 2).Figure 2


Functional metabolomics: from biomarker discovery to metabolome reprogramming.

Peng B, Li H, Peng XX - Protein Cell (2015)

Bacterial infection-sensitive metabolomeis reprogrammed to bacterial anti-infective metabolome by exogenous crucial metabolites. Sublethal dose of pathogen causes hosts either to die or survival, which is related to their metabolomes. Crucial metabolites can be identified by comparison of the two metabolomes. Exogenous addition of the crucial metabolites increases the chances of survival
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537470&req=5

Fig2: Bacterial infection-sensitive metabolomeis reprogrammed to bacterial anti-infective metabolome by exogenous crucial metabolites. Sublethal dose of pathogen causes hosts either to die or survival, which is related to their metabolomes. Crucial metabolites can be identified by comparison of the two metabolomes. Exogenous addition of the crucial metabolites increases the chances of survival
Mentions: Besides the reprogramming metabolome of immune regulator such as IFN-α2b, the approach can be used to restore host defense ability from susceptibility to resistance to pathogens. Streptococcosis causes massive tilapia kills, which results in heavy economic losses of tilapia farming industry. Current antibiotic options are limited and possess severe practical limitations and potential adverse environmental impacts. GC-MS based metabolomics is used to characterize variation of metabolomes in response to S. iniae. Nine key metabolites that separate the survivals from the dying and control were identified. N-acetylglucosamine was the most critical metabolite elevated in survival groups but decreased in dying groups. The reversal change formed a characteristic feature as a result of tilapias against infection caused by S. iniae. When exogenous N-acetylglucosamine was added, the survival ability significantly elevated by at least 35%. In anti-S. agalactiae metabolome, significant decrease of several amino acids and their metabolic pathways was characterized. L-proline was identified as a crucial biomarker. Three-day L-proline-supplemented tilapias by intraperitoneal injection or oral administration before challenging with S. agalactiae showed the significant higher resistance against the challenging bacteria, elevating 60% survival rates in group with 2 mg L-proline injection (Cheng et al., 2014). In the same way, the approach can be used to reprogram a metabolic strategy to modulate the effect of temperature on bacterial toxicity. S. agalactiae killed more tilapias in higher than lower temperatures, where 50% mortality and 70% mortality were reported for tilapias cultured in 25°C and 30°C, respectively while no death was detected at 20°C (Zhao et al., 2015). We investigated the metabolome change in the livers of tilapia. Thirty-six and forty-five varied abundance of metabolites were identified in livers of tilapias cultured at 25°C and 30°C, respectively. Decreasing abundance of L-proline was identified as a crucial biomarker for indexing higher water temperature and a potential modulator to reduce the high death. This was validated by engineering injection or oral addition of L-proline. Exogenous L-proline led to elevated amino acid metabolism, which contributed to the elevated survivals (Zhao et al., 2015). These results highlight the way to identify drug potentials to combat microbial infections though reprogramming metabolome (Fig. 2).Figure 2

Bottom Line: 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 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.This review introduces the current state and trends of discovery metabolomics and reprogramming metabolomics and highlights the importance of reprogramming metabolomics.

View Article: PubMed Central - PubMed

Affiliation: Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, CA, 94720, USA.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus