Aldehyde-alcohol dehydrogenase and/or thiolase overexpression coupled with CoA transferase downregulation lead to higher alcohol titers and selectivity in Clostridium acetobutylicum fermentations

Biotechnology and Bioengineering
Ryan SillersEleftherios T Papoutsakis

Abstract

Metabolic engineering (ME) of Clostridium acetobutylicum has led to increased solvent (butanol, acetone, and ethanol) production and solvent tolerance, thus demonstrating that further efforts have the potential to create strains of industrial importance. With recently developed ME tools, it is now possible to combine genetic modifications and thus implement more advanced ME strategies. We have previously shown that antisense RNA (asRNA)-based downregulation of CoA transferase (CoAT, the first enzyme in the acetone-formation pathway) results in increased butanol to acetone selectivity, but overall reduced butanol yields and titers. In this study the alcohol/aldehyde dehydrogenase (aad) gene (encoding the bifunctional protein AAD responsible for butanol and ethanol production from butyryl-CoA and acetyl-CoA, respectively) was expressed from the phosphotransbutyrylase (ptb) promoter to enhance butanol formation and selectivity, while CoAT downregulation was used to minimize acetone production. This led to early production of high alcohol (butanol plus ethanol) titers, overall solvent titers of 30 g/L, and a higher alcohol/acetone ratio. Metabolic flux analysis revealed the likely depletion of butyryl-CoA. In order to increase then...Continue Reading

References

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Citations

May 12, 2012·Applied Microbiology and Biotechnology·Dörte LehmannTina Lütke-Eversloh
Jul 11, 2012·Journal of Industrial Microbiology & Biotechnology·Erin GarzaShengde Zhou
Jan 3, 2012·Applied and Environmental Microbiology·Joungmin LeeSang Yup Lee
Feb 10, 2011·PloS One·Kaizhi JiaYin Li
May 13, 2014·Applied Microbiology and Biotechnology·Tina Lütke-Eversloh
Aug 17, 2010·Annual Review of Genetics·Maureen Kiley Thomason, Gisela Storz
Sep 18, 2012·Metabolic Engineering·Clare M CooksleyNigel P Minton
May 3, 2011·Metabolic Engineering·Mingrui YuShang-Tian Yang
Dec 8, 2010·Metabolic Engineering·Jungik Choi, Maciek R Antoniewicz
Oct 26, 2012·Biotechnology and Bioengineering·Miriam S Mann, Tina Lütke-Eversloh
Jun 23, 2011·Biotechnology Journal·Kevin V Solomon, Kristala L J Prather
Apr 9, 2015·Applied Microbiology and Biotechnology·Le YuShang-Tian Yang
May 9, 2013·Journal of Biotechnology·Xiaohu HouWeiguo Zhang
Mar 26, 2013·Metabolic Engineering·Michael Scheel, Tina Lütke-Eversloh
Nov 13, 2013·Metabolic Engineering·Ashwini BhandiwadLee R Lynd
Apr 29, 2014·Biotechnology Advances·Michael E PyneC Perry Chou
Aug 1, 2015·PloS One·Naama Tepper, Tomer Shlomi
Aug 18, 2016·Applied Microbiology and Biotechnology·Sang-Hyun LeeKyoung Heon Kim
Jan 1, 2012·Metabolites·Robert A Dromms, Mark P Styczynski

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