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The microbial reactome.

Ferrer M - Microb Biotechnol (2009)

View Article: PubMed Central - PubMed

Affiliation: CSIC - Institute of Catalysis, Madrid, Spain.

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Twenty years ago, you worked at the clean bench, you isolated new microbes able to grow on agar plates, and then you isolated single genes coding single enzymes for particular processes, you optimized them, and you wrote books or articles with conceptual and technical developments based on known biodiversity... But above all, there is the sense that biodiversity is at the centre of a vital scientific universe, with microbes as its capital: we know the communities, how diverse they are, but we are far from understanding the individual members and functions, and how each of them can be helpful, for example, to improve the human condition... It is like our human society: the government knows how many we are, but it does not know how each individual lives, and how many consortia (friends and family, to cite some) we constitute... The co‐founding editor of Microbial Microbiology wrote to me and asked, wouldn't I want entree into a crystal ball, to ‘predict’ the future and catch reader attention? By doing this, it will be possible to unravel gene functions and add valuable information about how microorganisms adapt to changing environmental influences, and how biotech processes can be designed by new microbial functions that can be checked by visualizing directly the reactomes... For example, bioinformatics methods exist for isolating in silico microbial reactomes; but they rely on sequence data... Metatranscriptomics has the potential to describe how metabolic activities will change, but still does not reflect the protein level and does not predict microbial functions (only upregulation or downregulation)... Finally, single‐cell genomics is increasing in importance but, once again, the sequencing of such cells will predict functions based on sequence data or, in the best case functional hypothesis of certain individual functions... So it does not need to take a crystal ball to see that the bottleneck in meta‐genomic technology, both for microbial and biotech point of view, will not be only the design of powerful assembler computer programs but rather the development of technologies that provide direct analysis of complex mixtures and entail detecting specific substrate‐protein transformations among thousands of other endogenous metabolites and proteins in order to get a clear picture of ‘who is doing what’... As Shakespeare said in Hamlet, ‘that is the question’! I think that this is the time to think about it as progress to manage sequence information per se accelerates... All in all, it is clear that to access the microbes in their natural milieu and new enzymes from them, there is a strong need to elaborate a Systems Biology concept based on the combination of multiple strategies to understand the functioning of microbial communities as a whole, with metagenomic tools playing a pivotal role (Fig.  1).

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A generalized Venn diagram with three sets of activities, (i) sampling processing and cell separation, (ii) DNA sequencing, annotation and analysis and (iii) functional (in terms of activity screens) and phylogenetic analysis, and their intersections. The interconnection among activities is crucial to get a proper analysis of microbial reactomes with Systems Biology implications.
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f1: A generalized Venn diagram with three sets of activities, (i) sampling processing and cell separation, (ii) DNA sequencing, annotation and analysis and (iii) functional (in terms of activity screens) and phylogenetic analysis, and their intersections. The interconnection among activities is crucial to get a proper analysis of microbial reactomes with Systems Biology implications.

Mentions: So it does not need to take a crystal ball to see that the bottleneck in meta‐genomic technology, both for microbial and biotech point of view, will not be only the design of powerful assembler computer programs but rather the development of technologies that provide direct analysis of complex mixtures and entail detecting specific substrate‐protein transformations among thousands of other endogenous metabolites and proteins in order to get a clear picture of ‘who is doing what’. Some methods do exist for isolating single transformations from the natural environment; but these are not relevant for reactome coverage as they are not universal. Clearly, existing methods for enzymatic activity detection based on changes in spectroscopic properties should give rise to high‐throughput chips than can be used to provide information on chemistry of reactions and identity of the product formed. This type of information will be extremely useful for ascribing functions to genetic sequences from environmental samples, thus minimizing annotation mistakes and suggesting biotechnological potential. I believe in a future where any single genome or environmental sequence project is done in parallel with chip‐based enzyme screening, so that annotations are experimentally documented at the time when the paper is written. Only through obtaining holistic information can holistic hypotheses about ecosystem characteristics be formulated. The question then is: ‘how many reaction and substrate types should one have in a single high‐throughput chip to cover the whole microbial metabolism’? As Shakespeare said in Hamlet, ‘that is the question’! I think that this is the time to think about it as progress to manage sequence information per se accelerates. All in all, it is clear that to access the microbes in their natural milieu and new enzymes from them, there is a strong need to elaborate a Systems Biology concept based on the combination of multiple strategies to understand the functioning of microbial communities as a whole, with metagenomic tools playing a pivotal role (Fig. 1).


The microbial reactome.

Ferrer M - Microb Biotechnol (2009)

A generalized Venn diagram with three sets of activities, (i) sampling processing and cell separation, (ii) DNA sequencing, annotation and analysis and (iii) functional (in terms of activity screens) and phylogenetic analysis, and their intersections. The interconnection among activities is crucial to get a proper analysis of microbial reactomes with Systems Biology implications.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3815820&req=5

f1: A generalized Venn diagram with three sets of activities, (i) sampling processing and cell separation, (ii) DNA sequencing, annotation and analysis and (iii) functional (in terms of activity screens) and phylogenetic analysis, and their intersections. The interconnection among activities is crucial to get a proper analysis of microbial reactomes with Systems Biology implications.
Mentions: So it does not need to take a crystal ball to see that the bottleneck in meta‐genomic technology, both for microbial and biotech point of view, will not be only the design of powerful assembler computer programs but rather the development of technologies that provide direct analysis of complex mixtures and entail detecting specific substrate‐protein transformations among thousands of other endogenous metabolites and proteins in order to get a clear picture of ‘who is doing what’. Some methods do exist for isolating single transformations from the natural environment; but these are not relevant for reactome coverage as they are not universal. Clearly, existing methods for enzymatic activity detection based on changes in spectroscopic properties should give rise to high‐throughput chips than can be used to provide information on chemistry of reactions and identity of the product formed. This type of information will be extremely useful for ascribing functions to genetic sequences from environmental samples, thus minimizing annotation mistakes and suggesting biotechnological potential. I believe in a future where any single genome or environmental sequence project is done in parallel with chip‐based enzyme screening, so that annotations are experimentally documented at the time when the paper is written. Only through obtaining holistic information can holistic hypotheses about ecosystem characteristics be formulated. The question then is: ‘how many reaction and substrate types should one have in a single high‐throughput chip to cover the whole microbial metabolism’? As Shakespeare said in Hamlet, ‘that is the question’! I think that this is the time to think about it as progress to manage sequence information per se accelerates. All in all, it is clear that to access the microbes in their natural milieu and new enzymes from them, there is a strong need to elaborate a Systems Biology concept based on the combination of multiple strategies to understand the functioning of microbial communities as a whole, with metagenomic tools playing a pivotal role (Fig. 1).

View Article: PubMed Central - PubMed

Affiliation: CSIC - Institute of Catalysis, Madrid, Spain.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

Twenty years ago, you worked at the clean bench, you isolated new microbes able to grow on agar plates, and then you isolated single genes coding single enzymes for particular processes, you optimized them, and you wrote books or articles with conceptual and technical developments based on known biodiversity... But above all, there is the sense that biodiversity is at the centre of a vital scientific universe, with microbes as its capital: we know the communities, how diverse they are, but we are far from understanding the individual members and functions, and how each of them can be helpful, for example, to improve the human condition... It is like our human society: the government knows how many we are, but it does not know how each individual lives, and how many consortia (friends and family, to cite some) we constitute... The co‐founding editor of Microbial Microbiology wrote to me and asked, wouldn't I want entree into a crystal ball, to ‘predict’ the future and catch reader attention? By doing this, it will be possible to unravel gene functions and add valuable information about how microorganisms adapt to changing environmental influences, and how biotech processes can be designed by new microbial functions that can be checked by visualizing directly the reactomes... For example, bioinformatics methods exist for isolating in silico microbial reactomes; but they rely on sequence data... Metatranscriptomics has the potential to describe how metabolic activities will change, but still does not reflect the protein level and does not predict microbial functions (only upregulation or downregulation)... Finally, single‐cell genomics is increasing in importance but, once again, the sequencing of such cells will predict functions based on sequence data or, in the best case functional hypothesis of certain individual functions... So it does not need to take a crystal ball to see that the bottleneck in meta‐genomic technology, both for microbial and biotech point of view, will not be only the design of powerful assembler computer programs but rather the development of technologies that provide direct analysis of complex mixtures and entail detecting specific substrate‐protein transformations among thousands of other endogenous metabolites and proteins in order to get a clear picture of ‘who is doing what’... As Shakespeare said in Hamlet, ‘that is the question’! I think that this is the time to think about it as progress to manage sequence information per se accelerates... All in all, it is clear that to access the microbes in their natural milieu and new enzymes from them, there is a strong need to elaborate a Systems Biology concept based on the combination of multiple strategies to understand the functioning of microbial communities as a whole, with metagenomic tools playing a pivotal role (Fig.  1).

Show MeSH
Related in: MedlinePlus