High density cultivation for efficient sesquiterpenoid biosynthesis in Synechocystis sp. PCC 6803
| Autor: | Oliver Mantovani, João S. Rodrigues, Dennis Dienst, Julian Wichmann, Pia Lindberg |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
0301 basic medicine Cyanobacteria lcsh:Medicine Biomass Cell Growth Processes Sesquiterpene Photosynthesis Microbiology 01 natural sciences Article 03 medical and health sciences chemistry.chemical_compound Biosynthesis 010608 biotechnology Alkanes Food science lcsh:Science Multidisciplinary biology Phototroph lcsh:R Biochemistry and Molecular Biology Synechocystis biology.organism_classification Terpenoid Monocyclic Sesquiterpenes Mikrobiologi Metabolic pathway Phototrophic Processes 030104 developmental biology Synechocystis sp Metabolic Engineering chemistry lcsh:Q Bisabolene Sesquiterpenes Biokemi och molekylärbiologi Biotechnology |
| Zdroj: | Scientific Reports Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-020-62681-w |
| Popis: | Cyanobacteria and microalgae are attractive phototrophic host systems for climate-friendly production of fuels and other high-value chemicals. The biosynthesis of an increasing diversity of industrially relevant compounds such as terpenoids has been demonstrated in recent years. To develop economically feasible and sustainable process designs, major challenges still remain regarding intracellular carbon partitioning, specific metabolic pathway activities and efficient cultivation strategies. Here, we present a technical study on comparative characteristics of sesquiterpene and sesquiterpene alcohol accumulation in engineered strains ofSynechocystissp. PCC 6803 (substrain GT-U) under different growth conditions and cell densities. This study particularly focuses on the basic applicability of a commercial High Density Cultivation platform in the presence of a dodecane overlay, which serves as a standardin-situextractant and sink for various hydrophobic biochemicals. Significantly, the presented data demonstrate high volumetric productivities of (E)-α-bisabolene under high-density conditions that are more than two orders of magnitude higher than previously reported for cyanobacteria. Operating in a two-step semi-batch mode over a period of eight days, average final volumetric titers of 179.4 ± 20.7 mg * L−1were detected. Likewise, the sesquiterpene alcohols (-)-patchoulol and (-)-α-bisabolol accumulated to many times higher levels in high density cultivation than under standard batch conditions, with final titers of 17.3 ± 1.85 mg * L−1and 96.3 ± 2.2 mg * L−1, respectively. In contrast, specific product accumulation (mg * L−1* OD750−1) was compromised particularly for bisabolene in the high density system during phases of high biomass accumulation rates. Volumetric productivities were high during linear growth at high densities, distinctly outperforming standard batch systems. While the presented data highlight the benefits of high-density strategies for highly efficient phototrophic terpenoid production, they further point at the presence of major metabolic bottlenecks for engineered terpenoid biosynthesis and the requirement for systematic and/or targeted strategies to sustainably redirect inherent carbon fluxes in cyanobacteria. Together, our data provide additional insights into growth- and density-related effects on the efficiency of product accumulation, introducing low-scale High Density Cultivation as a rapid and efficient platform for screening of heterologous terpenoid production in cyanobacteria. |
| Databáze: | OpenAIRE |
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