This title appears in the Scientific Report :
2019
Please use the identifier:
http://dx.doi.org/10.1007/s00253-019-10121-9 in citations.
Please use the identifier: http://hdl.handle.net/2128/23492 in citations.
Microbial synthesis of the type I polyketide 6-methylsalicylate with Corynebacterium glutamicum
Microbial synthesis of the type I polyketide 6-methylsalicylate with Corynebacterium glutamicum
Type I polyketide synthases (PKSs) are large multi-domain proteins converting simple acyl-CoA thioesters such as acetyl-CoA and malonyl-CoA to a large diversity of biotechnologically interesting molecules. Such multi-step reaction cascades are of particular interest for applications in engineered mi...
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Personal Name(s): | Kallscheuer, Nicolai |
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Kage, Hirokazu / Milke, Lars / Nett, Markus / Marienhagen, Jan (Corresponding author) | |
Contributing Institute: |
Biotechnologie; IBG-1 |
Published in: | Applied microbiology and biotechnology, 103 (2019) 23-24, S. 9619 - 9631 |
Imprint: |
New York
Springer
2019
|
DOI: |
10.1007/s00253-019-10121-9 |
PubMed ID: |
31686146 |
Document Type: |
Journal Article |
Research Program: |
Innovative Synergisms |
Link: |
Restricted Published on 2019-11-04. Available in OpenAccess from 2020-11-04. Published on 2019-11-04. Available in OpenAccess from 2020-11-04. Restricted |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/23492 in citations.
Type I polyketide synthases (PKSs) are large multi-domain proteins converting simple acyl-CoA thioesters such as acetyl-CoA and malonyl-CoA to a large diversity of biotechnologically interesting molecules. Such multi-step reaction cascades are of particular interest for applications in engineered microbial cell factories, as the introduction of a single protein with many enzymatic activities does not require balancing of several individual enzymatic activities. However, functional introduction of type I PKSs into heterologous hosts is very challenging as the large polypeptide chains often do not fold properly. In addition, PKS usually require post-translational activation by dedicated 4′-phosphopantetheinyl transferases (PPTases). Here, we introduce an engineered Corynebacterium glutamicum strain as a novel microbial cell factory for type I PKS-derived products. Suitability of C. glutamicum for polyketide synthesis could be demonstrated by the functional introduction of the 6-methylsalicylic acid synthase ChlB1 from Streptomyces antibioticus. Challenges related to protein folding could be overcome by translation fusion of ChlB1Sa to the C-terminus of the maltose-binding protein MalE from Escherichia coli. Surprisingly, ChlB1Sa was also active in the absence of a heterologous PPTase, which finally led to the discovery that the endogenous PPTase PptACg of C. glutamicum can also activate ChlB1Sa. The best strain, engineered to provide increased levels of acetyl-CoA and malonyl-CoA, accumulated up to 41 mg/L (0.27 mM) 6-methylsalicylic acid within 48 h of cultivation. Further experiments showed that PptACg of C. glutamicum can also activate nonribosomal peptide synthetases (NRPSs), rendering C. glutamicum a promising microbial cell factory for the production of several fine chemicals and medicinal drugs |