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Effects of acetoacetyl-CoA synthase expression on production of farnesene in Saccharomyces cerevisiae

Stefan Tippmann (Institutionen för biologi och bioteknik, Systembiologi) ; Raphael Ferreira (Institutionen för biologi och bioteknik, Systembiologi) ; Verena Siewers (Institutionen för biologi och bioteknik, Systembiologi) ; Jens B. Nielsen (Institutionen för biologi och bioteknik, Systembiologi) ; Yun Chen (Institutionen för biologi och bioteknik, Systembiologi)
Journal of Industrial Microbiology and Biotechnology (13675435). Vol. 44 (2017), 6, p. 911-922.
[Artikel, refereegranskad vetenskaplig]

Efficient production of sesquiterpenes in Saccharomyces cerevisiae requires a high flux through the mevalonate pathway. To achieve this, the supply of acetyl-CoA plays a crucial role, partially because nine moles of acetyl-CoA are necessary to produce one mole of farnesyl diphosphate, but also to overcome the thermodynamic constraint imposed on the first reaction, in which acetoacetyl-CoA is produced from two moles of acetyl-CoA by acetoacetyl-CoA thiolase. Recently, a novel acetoacetyl-CoA synthase (nphT7) has been identified from Streptomyces sp. strain CL190, which catalyzes the irreversible condensation of malonyl-CoA and acetyl-CoA to acetoacetyl-CoA and, therefore, represents a potential target to increase the flux through the mevalonate pathway. This study investigates the effect of acetoacetyl-CoA synthase on growth as well as the production of farnesene and compares different homologs regarding their efficiency. While plasmid-based expression of nphT7 did not improve final farnesene titers, the construction of an alternative pathway, which exclusively relies on the malonyl-CoA bypass, was detrimental for growth and farnesene production. The presented results indicate that the overall functionality of the bypass was limited by the efficiency of acetoacetyl-CoA synthase (nphT7). Besides modulation of the expression level, which could be used as a means to partially restore the phenotype, nphT7 from Streptomyces glaucescens showed clearly higher efficiency compared to Streptomyces sp. strain CL190. © 2017, The Author(s).

Nyckelord: Biofuels; Isoprenoids; Metabolic engineering; Mevalonate pathway; Yeast



Denna post skapades 2017-06-14. Senast ändrad 2017-07-11.
CPL Pubid: 249831

 

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Institutioner (Chalmers)

Institutionen för biologi och bioteknik, Systembiologi

Ämnesområden

Biokemi och molekylärbiologi
Mikrobiologi

Chalmers infrastruktur