Probing the heterologous metabolism supporting 6-deoxyerythronolide B biosynthesis in Escherichia coli

Haoran Zhang; Yong Wang; Brett Boghigian; Blaine A. Pfeifer

doi:https://doi.org/10.1111/j.1751-7915.2009.00099.x

Probing the heterologous metabolism supporting 6-deoxyerythronolide B biosynthesis in Escherichia coli

Haoran Zhang, Yong Wang, Brett Boghigian, Blaine A. Pfeifer

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Heterologous biosynthesis offers a new way to capture the medicinal properties presented by complex natural products. In this study, production of 6-deoxyerythronolide B (6dEB), the polyketide precursor to the antibiotic erythromycin, was used to probe the heterologous pathways needed for Escherichia coli-derived biosynthesis. More specifically, the heterologous proteins responsible for 6dEB production were varied by adjusting their respective gene dosage levels. In this way, heterologous components required for posttranslational modification, 6dEB biosynthesis, and substrate provision were adjusted in expression levels to observe the relative effect each has on final heterologous biosynthesis. The results indicate that both the biosynthetic and substrate provision heterologous proteins impact 6dEB formation to a greater extent when compared with posttranslational modification and suggest these components for future protein and metabolic engineering.

Original language	English (US)
Pages (from-to)	390-394
Number of pages	5
Journal	Microbial Biotechnology
Volume	2
Issue number	3
DOIs	https://doi.org/10.1111/j.1751-7915.2009.00099.x
State	Published - May 2009
Externally published	Yes

ASJC Scopus subject areas

Biotechnology
Bioengineering
Biochemistry
Applied Microbiology and Biotechnology

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title = "Probing the heterologous metabolism supporting 6-deoxyerythronolide B biosynthesis in Escherichia coli",

abstract = "Heterologous biosynthesis offers a new way to capture the medicinal properties presented by complex natural products. In this study, production of 6-deoxyerythronolide B (6dEB), the polyketide precursor to the antibiotic erythromycin, was used to probe the heterologous pathways needed for Escherichia coli-derived biosynthesis. More specifically, the heterologous proteins responsible for 6dEB production were varied by adjusting their respective gene dosage levels. In this way, heterologous components required for posttranslational modification, 6dEB biosynthesis, and substrate provision were adjusted in expression levels to observe the relative effect each has on final heterologous biosynthesis. The results indicate that both the biosynthetic and substrate provision heterologous proteins impact 6dEB formation to a greater extent when compared with posttranslational modification and suggest these components for future protein and metabolic engineering.",

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AU - Boghigian, Brett

AU - Pfeifer, Blaine A.

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AB - Heterologous biosynthesis offers a new way to capture the medicinal properties presented by complex natural products. In this study, production of 6-deoxyerythronolide B (6dEB), the polyketide precursor to the antibiotic erythromycin, was used to probe the heterologous pathways needed for Escherichia coli-derived biosynthesis. More specifically, the heterologous proteins responsible for 6dEB production were varied by adjusting their respective gene dosage levels. In this way, heterologous components required for posttranslational modification, 6dEB biosynthesis, and substrate provision were adjusted in expression levels to observe the relative effect each has on final heterologous biosynthesis. The results indicate that both the biosynthetic and substrate provision heterologous proteins impact 6dEB formation to a greater extent when compared with posttranslational modification and suggest these components for future protein and metabolic engineering.

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Probing the heterologous metabolism supporting 6-deoxyerythronolide B biosynthesis in Escherichia coli

Abstract

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