High-level production of ethylmalonyl-CoA pathway-derived dicarboxylic acids by Methylobacterium extorquens under cobalt-deficient conditions and by polyhydroxybutyrate negative strains
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| 024 | 7 | 0 | |a 10.1007/s00253-015-6418-3 |2 doi |
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| 245 | 0 | 0 | |a High-level production of ethylmalonyl-CoA pathway-derived dicarboxylic acids by Methylobacterium extorquens under cobalt-deficient conditions and by polyhydroxybutyrate negative strains |h [Elektronische Daten] |c [Frank Sonntag, Jonas Müller, Patrick Kiefer, Julia Vorholt, Jens Schrader, Markus Buchhaupt] |
| 520 | 3 | |a Bio-based production of dicarboxylic acids is an emerging research field with remarkable progress during the last decades. The recently established synthesis of the ethylmalonyl-CoA pathway (EMCP)-derived dicarboxylic acids, mesaconic acid and (2S)-methylsuccinic acid, from the alternative carbon source methanol (Sonntag et al., Appl Microbiol Biotechnol 98:4533-4544, 2014) gave a proof of concept for the sustainable production of hitherto biotechnologically inaccessible monomers. In this study, substantial optimizations of the process by different approaches are presented. Abolishment of mesaconic and (2S)-methylsuccinic acid reuptake from culture supernatant and a productivity increase were achieved by 30-fold decreased sodium ion availability in culture medium. Undesired flux from EMCP into polyhydroxybutyrate (PHB) cycle was hindered by the knockout of polyhydroxyalkanoate synthase phaC which was concomitant with 5-fold increased product concentrations. However, frequently occurring suppressors of strain ΔphaC lost their beneficial properties probably due to redirected channeling of acetyl-CoA. Pool sizes of the product precursors were increased by exploiting the presence of two cobalt-dependent mutases in the EMCP: Fine-tuned growth-limiting cobalt concentrations led to 16-fold accumulation of mesaconyl- and (2S)-methylsuccinyl-CoA which in turn resulted in 6-fold increased concentrations of mesaconic and (2S)-methylsuccinic acids, with a combined titer of 0.65g/l, representing a yield of 0.17g/g methanol. This work represents an important step toward an industrially relevant production of ethylmalonyl-CoA pathway-derived dicarboxylic acids and the generation of a stable PHB synthesis negative Methylobacterium extorquens strain. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Dicarboxylic acids |2 nationallicence | |
| 690 | 7 | |a Ethylmalonyl-CoA pathway |2 nationallicence | |
| 690 | 7 | |a Methylobacterium extorquens |2 nationallicence | |
| 690 | 7 | |a Methanol |2 nationallicence | |
| 690 | 7 | |a PHB |2 nationallicence | |
| 700 | 1 | |a Sonntag |D Frank |u DECHEMA Research Institute, Theodor-Heuss-Allee 25, 60486, Frankfurt am Main, Germany |4 aut | |
| 700 | 1 | |a Müller |D Jonas |u Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland |4 aut | |
| 700 | 1 | |a Kiefer |D Patrick |u Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland |4 aut | |
| 700 | 1 | |a Vorholt |D Julia |u Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland |4 aut | |
| 700 | 1 | |a Schrader |D Jens |u DECHEMA Research Institute, Theodor-Heuss-Allee 25, 60486, Frankfurt am Main, Germany |4 aut | |
| 700 | 1 | |a Buchhaupt |D Markus |u DECHEMA Research Institute, Theodor-Heuss-Allee 25, 60486, Frankfurt am Main, Germany |4 aut | |
| 773 | 0 | |t Applied Microbiology and Biotechnology |d Springer Berlin Heidelberg |g 99/8(2015-04-01), 3407-3419 |x 0175-7598 |q 99:8<3407 |1 2015 |2 99 |o 253 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00253-015-6418-3 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00253-015-6418-3 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Sonntag |D Frank |u DECHEMA Research Institute, Theodor-Heuss-Allee 25, 60486, Frankfurt am Main, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Müller |D Jonas |u Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kiefer |D Patrick |u Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Vorholt |D Julia |u Institute of Microbiology, ETH Zurich, Vladimir-Prelog-Weg 4, 8093, Zurich, Switzerland |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Schrader |D Jens |u DECHEMA Research Institute, Theodor-Heuss-Allee 25, 60486, Frankfurt am Main, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Buchhaupt |D Markus |u DECHEMA Research Institute, Theodor-Heuss-Allee 25, 60486, Frankfurt am Main, Germany |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Applied Microbiology and Biotechnology |d Springer Berlin Heidelberg |g 99/8(2015-04-01), 3407-3419 |x 0175-7598 |q 99:8<3407 |1 2015 |2 99 |o 253 | ||