Low potency toxins reveal dense interaction networks in metabolism
Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved....
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| Format: | Article |
| Language: | English |
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BioMed Central
2016
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| Online Access: | http://hdl.handle.net/1721.1/101233 |
| _version_ | 1826215398147620864 |
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| author | Bains, William |
| author2 | Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences Bains, William |
| author_sort | Bains, William |
| collection | MIT |
| description | Background
The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs.
Results
Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function.
Conclusions
The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved. |
| first_indexed | 2024-09-23T16:27:14Z |
| format | Article |
| id | mit-1721.1/101233 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:27:14Z |
| publishDate | 2016 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1012332022-10-02T08:03:49Z Low potency toxins reveal dense interaction networks in metabolism Bains, William Massachusetts Institute of Technology. Department of Earth, Atmospheric, and Planetary Sciences Bains, William Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved. 2016-02-23T00:11:02Z 2016-02-23T00:11:02Z 2016-02 2015-06 2016-02-21T05:45:15Z Article http://purl.org/eprint/type/JournalArticle 1752-0509 http://hdl.handle.net/1721.1/101233 Bains, William. “Low Potency Toxins Reveal Dense Interaction Networks in Metabolism.” BMC Syst Biol 10, no. 1 (February 20, 2016). en http://dx.doi.org/10.1186/s12918-016-0262-7 BMC Systems Biology Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ Bains. application/pdf BioMed Central BioMed Central |
| spellingShingle | Bains, William Low potency toxins reveal dense interaction networks in metabolism |
| title | Low potency toxins reveal dense interaction networks in metabolism |
| title_full | Low potency toxins reveal dense interaction networks in metabolism |
| title_fullStr | Low potency toxins reveal dense interaction networks in metabolism |
| title_full_unstemmed | Low potency toxins reveal dense interaction networks in metabolism |
| title_short | Low potency toxins reveal dense interaction networks in metabolism |
| title_sort | low potency toxins reveal dense interaction networks in metabolism |
| url | http://hdl.handle.net/1721.1/101233 |
| work_keys_str_mv | AT bainswilliam lowpotencytoxinsrevealdenseinteractionnetworksinmetabolism |