Cargando…
Heterologous Production of 6-Deoxyerythronolide B in Escherichia coli through the Wood Werkman Cycle
Polyketides are a remarkable class of natural products with diverse functional and structural diversity. The class includes many medicinally important molecules with antiviral, antimicrobial, antifungal and anticancer properties. Native bacterial, fungal and plant hosts are often difficult to cultiv...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344785/ https://www.ncbi.nlm.nih.gov/pubmed/32492827 http://dx.doi.org/10.3390/metabo10060228 |
_version_ | 1783556025675153408 |
---|---|
author | Gonzalez-Garcia, R. Axayacatl Nielsen, Lars K. Marcellin, Esteban |
author_facet | Gonzalez-Garcia, R. Axayacatl Nielsen, Lars K. Marcellin, Esteban |
author_sort | Gonzalez-Garcia, R. Axayacatl |
collection | PubMed |
description | Polyketides are a remarkable class of natural products with diverse functional and structural diversity. The class includes many medicinally important molecules with antiviral, antimicrobial, antifungal and anticancer properties. Native bacterial, fungal and plant hosts are often difficult to cultivate and coax into producing the desired product. As a result, Escherichia coli has been used for the heterologous production of polyketides, with the production of 6-deoxyerythronolide B (6-dEB) being the first example. Current strategies for production in E. coli require feeding of exogenous propionate as a source for the precursors propionyl-CoA and S-methylmalonyl-CoA. Here, we show that heterologous polyketide production is possible from glucose as the sole carbon source. The heterologous expression of eight genes from the Wood-Werkman cycle found in Propionibacteria, in combination with expression of the 6-dEB synthases DEBS1, DEBS2 and DEBS3 resulted in 6-dEB formation from glucose as the sole carbon source. Our results show that the Wood-Werkman cycle provides the required propionyl-CoA and the extender unit S-methylmalonyl-CoA to produce up to 0.81 mg/L of 6-dEB in a chemically defined media. |
format | Online Article Text |
id | pubmed-7344785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73447852020-07-09 Heterologous Production of 6-Deoxyerythronolide B in Escherichia coli through the Wood Werkman Cycle Gonzalez-Garcia, R. Axayacatl Nielsen, Lars K. Marcellin, Esteban Metabolites Article Polyketides are a remarkable class of natural products with diverse functional and structural diversity. The class includes many medicinally important molecules with antiviral, antimicrobial, antifungal and anticancer properties. Native bacterial, fungal and plant hosts are often difficult to cultivate and coax into producing the desired product. As a result, Escherichia coli has been used for the heterologous production of polyketides, with the production of 6-deoxyerythronolide B (6-dEB) being the first example. Current strategies for production in E. coli require feeding of exogenous propionate as a source for the precursors propionyl-CoA and S-methylmalonyl-CoA. Here, we show that heterologous polyketide production is possible from glucose as the sole carbon source. The heterologous expression of eight genes from the Wood-Werkman cycle found in Propionibacteria, in combination with expression of the 6-dEB synthases DEBS1, DEBS2 and DEBS3 resulted in 6-dEB formation from glucose as the sole carbon source. Our results show that the Wood-Werkman cycle provides the required propionyl-CoA and the extender unit S-methylmalonyl-CoA to produce up to 0.81 mg/L of 6-dEB in a chemically defined media. MDPI 2020-06-01 /pmc/articles/PMC7344785/ /pubmed/32492827 http://dx.doi.org/10.3390/metabo10060228 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gonzalez-Garcia, R. Axayacatl Nielsen, Lars K. Marcellin, Esteban Heterologous Production of 6-Deoxyerythronolide B in Escherichia coli through the Wood Werkman Cycle |
title | Heterologous Production of 6-Deoxyerythronolide B in Escherichia coli through the Wood Werkman Cycle |
title_full | Heterologous Production of 6-Deoxyerythronolide B in Escherichia coli through the Wood Werkman Cycle |
title_fullStr | Heterologous Production of 6-Deoxyerythronolide B in Escherichia coli through the Wood Werkman Cycle |
title_full_unstemmed | Heterologous Production of 6-Deoxyerythronolide B in Escherichia coli through the Wood Werkman Cycle |
title_short | Heterologous Production of 6-Deoxyerythronolide B in Escherichia coli through the Wood Werkman Cycle |
title_sort | heterologous production of 6-deoxyerythronolide b in escherichia coli through the wood werkman cycle |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344785/ https://www.ncbi.nlm.nih.gov/pubmed/32492827 http://dx.doi.org/10.3390/metabo10060228 |
work_keys_str_mv | AT gonzalezgarciaraxayacatl heterologousproductionof6deoxyerythronolidebinescherichiacolithroughthewoodwerkmancycle AT nielsenlarsk heterologousproductionof6deoxyerythronolidebinescherichiacolithroughthewoodwerkmancycle AT marcellinesteban heterologousproductionof6deoxyerythronolidebinescherichiacolithroughthewoodwerkmancycle |