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...

Descripción completa

Detalles Bibliográficos
Autores principales: Gonzalez-Garcia, R. Axayacatl, Nielsen, Lars K., Marcellin, Esteban
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