Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs.
Synthetic microbial consortia have been increasingly utilized in biotechnology and experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, though, a quantitative understanding of the con...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-04-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1007795 |
| _version_ | 1818578164322926592 |
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| author | Marco Mauri Jean-Luc Gouzé Hidde de Jong Eugenio Cinquemani |
| author_facet | Marco Mauri Jean-Luc Gouzé Hidde de Jong Eugenio Cinquemani |
| author_sort | Marco Mauri |
| collection | DOAJ |
| description | Synthetic microbial consortia have been increasingly utilized in biotechnology and experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, though, a quantitative understanding of the conditions that make this possible, and of the trade-offs due to the concurrent growth of multiple species, is still limited. In this work, we contribute to filling this gap by the investigation of a known prototypical synthetic consortium. A first E. coli strain, producing a heterologous protein, is sided by a second E. coli strain engineered to scavenge toxic byproducts, thus favoring the growth of the producer at the expense of diverting part of the resources to the growth of the cleaner. The simplicity of the consortium is ideal to perform an in depth-analysis and draw conclusions of more general interest. We develop a coarse-grained mathematical model that quantitatively accounts for literature data from different key growth phenotypes. Based on this, assuming growth in chemostat, we first investigate the conditions enabling stable coexistence of both strains and the effect of the metabolic load due to heterologous protein production. In these conditions, we establish when and to what extent the consortium outperforms the producer alone in terms of productivity. Finally, we show in chemostat as well as in a fed-batch scenario that gain in productivity comes at the price of a reduced yield, reflecting at the level of the consortium resource allocation trade-offs that are well-known for individual species. |
| first_indexed | 2024-12-16T06:41:27Z |
| format | Article |
| id | doaj.art-a32739c85d21462893de01cf9711d749 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-16T06:41:27Z |
| publishDate | 2020-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-a32739c85d21462893de01cf9711d7492022-12-21T22:40:41ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582020-04-01164e100779510.1371/journal.pcbi.1007795Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs.Marco MauriJean-Luc GouzéHidde de JongEugenio CinquemaniSynthetic microbial consortia have been increasingly utilized in biotechnology and experimental evidence shows that suitably engineered consortia can outperform individual species in the synthesis of valuable products. Despite significant achievements, though, a quantitative understanding of the conditions that make this possible, and of the trade-offs due to the concurrent growth of multiple species, is still limited. In this work, we contribute to filling this gap by the investigation of a known prototypical synthetic consortium. A first E. coli strain, producing a heterologous protein, is sided by a second E. coli strain engineered to scavenge toxic byproducts, thus favoring the growth of the producer at the expense of diverting part of the resources to the growth of the cleaner. The simplicity of the consortium is ideal to perform an in depth-analysis and draw conclusions of more general interest. We develop a coarse-grained mathematical model that quantitatively accounts for literature data from different key growth phenotypes. Based on this, assuming growth in chemostat, we first investigate the conditions enabling stable coexistence of both strains and the effect of the metabolic load due to heterologous protein production. In these conditions, we establish when and to what extent the consortium outperforms the producer alone in terms of productivity. Finally, we show in chemostat as well as in a fed-batch scenario that gain in productivity comes at the price of a reduced yield, reflecting at the level of the consortium resource allocation trade-offs that are well-known for individual species.https://doi.org/10.1371/journal.pcbi.1007795 |
| spellingShingle | Marco Mauri Jean-Luc Gouzé Hidde de Jong Eugenio Cinquemani Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs. PLoS Computational Biology |
| title | Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs. |
| title_full | Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs. |
| title_fullStr | Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs. |
| title_full_unstemmed | Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs. |
| title_short | Enhanced production of heterologous proteins by a synthetic microbial community: Conditions and trade-offs. |
| title_sort | enhanced production of heterologous proteins by a synthetic microbial community conditions and trade offs |
| url | https://doi.org/10.1371/journal.pcbi.1007795 |
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