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Distributing a metabolic pathway among a microbial consortium enhances production of natural products
Metabolic engineering of microorganisms such as Escherichia coli and Saccharomyces cerevisiae to produce high-value natural metabolites is often done through functional reconstitution of long metabolic pathways. Problems arise when parts of pathways require specialized environments or compartments f...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867547/ https://www.ncbi.nlm.nih.gov/pubmed/25558867 http://dx.doi.org/10.1038/nbt.3095 |
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author | Zhou, Kang Qiao, Kangjian Edgar, Steven Stephanopoulos, Gregory |
author_facet | Zhou, Kang Qiao, Kangjian Edgar, Steven Stephanopoulos, Gregory |
author_sort | Zhou, Kang |
collection | PubMed |
description | Metabolic engineering of microorganisms such as Escherichia coli and Saccharomyces cerevisiae to produce high-value natural metabolites is often done through functional reconstitution of long metabolic pathways. Problems arise when parts of pathways require specialized environments or compartments for optimal function. Here we solve this problem through co-culture of engineered organisms, each of which contains the part of the pathway that it is best suited to hosting. In one example, we divided the synthetic pathway for the acetylated diol paclitaxel precursor into two modules, expressed in either S. cerevisiae or E. coli, neither of which can produce the paclitaxel precursor on their own. Stable co-culture in the same bioreactor was achieved by designing a mutualistic relationship between the two species in which a metabolic intermediate produced by E. coli was used and functionalized by yeast. This synthetic consortium produced 33 mg/L oxygenated taxanes, including a monoacetylated dioxygenated taxane. The same method was also used to produce tanshinone precursors and functionalized sesquiterpenes. |
format | Online Article Text |
id | pubmed-4867547 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48675472016-05-16 Distributing a metabolic pathway among a microbial consortium enhances production of natural products Zhou, Kang Qiao, Kangjian Edgar, Steven Stephanopoulos, Gregory Nat Biotechnol Article Metabolic engineering of microorganisms such as Escherichia coli and Saccharomyces cerevisiae to produce high-value natural metabolites is often done through functional reconstitution of long metabolic pathways. Problems arise when parts of pathways require specialized environments or compartments for optimal function. Here we solve this problem through co-culture of engineered organisms, each of which contains the part of the pathway that it is best suited to hosting. In one example, we divided the synthetic pathway for the acetylated diol paclitaxel precursor into two modules, expressed in either S. cerevisiae or E. coli, neither of which can produce the paclitaxel precursor on their own. Stable co-culture in the same bioreactor was achieved by designing a mutualistic relationship between the two species in which a metabolic intermediate produced by E. coli was used and functionalized by yeast. This synthetic consortium produced 33 mg/L oxygenated taxanes, including a monoacetylated dioxygenated taxane. The same method was also used to produce tanshinone precursors and functionalized sesquiterpenes. 2015-01-05 2015-04 /pmc/articles/PMC4867547/ /pubmed/25558867 http://dx.doi.org/10.1038/nbt.3095 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Zhou, Kang Qiao, Kangjian Edgar, Steven Stephanopoulos, Gregory Distributing a metabolic pathway among a microbial consortium enhances production of natural products |
title | Distributing a metabolic pathway among a microbial consortium enhances production of natural products |
title_full | Distributing a metabolic pathway among a microbial consortium enhances production of natural products |
title_fullStr | Distributing a metabolic pathway among a microbial consortium enhances production of natural products |
title_full_unstemmed | Distributing a metabolic pathway among a microbial consortium enhances production of natural products |
title_short | Distributing a metabolic pathway among a microbial consortium enhances production of natural products |
title_sort | distributing a metabolic pathway among a microbial consortium enhances production of natural products |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4867547/ https://www.ncbi.nlm.nih.gov/pubmed/25558867 http://dx.doi.org/10.1038/nbt.3095 |
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