Dynamic control of gene expression in Saccharomyces cerevisiae engineered for the production of plant sesquitepene α-santalene in a fed-batch mode

Metabolic Engineering
Gionata ScalcinatiVerena Siewers

Abstract

Microbial cells engineered for efficient production of plant sesquiterpenes may allow for sustainable and scalable production of these compounds that can be used as e.g. perfumes and pharmaceuticals. Here, for the first time a Saccharomyces cerevisiae strain capable of producing high levels of α-santalene, the precursor of a commercially interesting compound, was constructed through a rationally designed metabolic engineering approach. Optimal sesquiterpene production was obtained by modulating the expression of one of the key metabolic steps of the mevalonate (MVA) pathway, squalene synthase (Erg9). To couple ERG9 expression to glucose concentration its promoter was replaced by the HXT1 promoter. In a second approach, the HXT2 promoter was used to express an ERG9 antisense construct. Using the HXT1 promoter to control ERG9 expression, it was possible to divert the carbon flux from sterol synthesis towards α-santalene improving the productivity by 3.4 fold. Combining this approach together with the overexpression of a truncated form of 3-hydroxyl-3-methyl-glutaryl-CoA reductase (HMGR) and deletion of lipid phosphate phosphatase encoded by LPP1 led to a strain with a productivity of 0.18mg/gDCWh. The titer was further increased ...Continue Reading

References

Jun 1, 1991·Current Opinion in Biotechnology·A J Daugulis
Feb 1, 1990·Nature·J L Goldstein, M S Brown
Jul 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·S M JenningsG W Robinson
Aug 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·M E BassonJ Rine
May 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·T J Scallen, A Sanghvi
Jun 1, 1994·Bioscience, Biotechnology, and Biochemistry·S YamanoN Misawa
Dec 1, 1994·Archives of Biochemistry and Biophysics·V S Bansal, S Vaidya
Jul 1, 1996·Nucleic Acids Research·U GüldenerJ H Hegemann
Apr 1, 1996·Trends in Biochemical Sciences·R HamptonJ Rine
Apr 1, 1997·Current Opinion in Biotechnology·A J Daugulis
Dec 1, 1996·Yeast·J T PronkJ P Van Dijken
Jan 24, 1998·Genome Research·N ErdenizR Rothstein
Mar 6, 1998·Applied Microbiology and Biotechnology·T PolakowskiC Lang
Feb 5, 2003·Genome Research·Jochen FörsterJens Nielsen
May 9, 2003·Organic Letters·Beth E JacksonSeiichi P T Matsuda
May 22, 2003·Analytical Biochemistry·Linsheng Song
Mar 3, 2004·Journal of Chromatography. a·Melanie-Jayne R HowesGeoffrey C Kite
Mar 31, 2005·Archives of Biochemistry and Biophysics·Sarah PicaudPeter E Brodelius
Jun 18, 2005·Current Opinion in Biotechnology·Ivan MijakovicPeter Ruhdal Jensen
Aug 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hal AlperGregory Stephanopoulos
Sep 15, 2005·Biotechnology and Bioengineering·JingHong M DejongRodney B Croteau
Dec 14, 2005·Biochemical and Biophysical Research Communications·M BonoliA Hochkoeppler
Jan 13, 2006·Trends in Biotechnology·Karin HammerPeter Ruhdal Jensen
Jun 1, 2006·Biotechnology and Bioengineering·M JeudeJ Büchs
Aug 4, 2006·Applied and Environmental Microbiology·Elke NevoigtGregory Stephanopoulos
Oct 3, 2006·Biotechnology and Bioengineering·Shunji TakahashiJoe Chappell
Nov 17, 2006·Nature Chemical Biology·Michelle C Y Chang, Jay D Keasling
Nov 23, 2006·Applied Microbiology and Biotechnology·Sydnor T Withers, Jay D Keasling
Aug 21, 2007·Biotechnology and Bioengineering·Mohammad A AsadollahiJens Nielsen
Oct 24, 2007·Methods in Enzymology·George M Carman, Wen-I Wu
Jan 5, 2008·Biotechnology and Bioengineering·Eric M ParadiseJay D Keasling
Mar 22, 2008·Molecular Pharmaceutics·Parayil Kumaran AjikumarGregory Stephanopoulos

❮ Previous
Next ❯

Citations

Jan 10, 2014·Microbial Cell Factories·Katrin WeinhandlAndrea Camattari
Dec 17, 2014·Microbial Cell Factories·Kiyotaka Y HaraAkihiko Kondo
May 1, 2013·Current Opinion in Chemical Biology·Nicolaas A BuijsJens Nielsen
Feb 2, 2015·Metabolic Engineering·Tadas JakočiūnasJay D Keasling
Nov 29, 2015·Biotechnology Letters·Pegah AmiriSiavash Partow
Mar 12, 2016·Cell·Jens Nielsen, Jay D Keasling
Mar 5, 2014·Plant, Cell & Environment·Claudia E VickersHarro Bouwmeester
Nov 7, 2015·ACS Synthetic Biology·Sue Zanne TanKristala L J Prather
Apr 6, 2016·Journal of Biotechnology·Anita Emmerstorfer-AugustinHarald Pichler
Apr 2, 2013·Current Opinion in Biotechnology·Leqian LiuHal S Alper
Feb 4, 2014·Current Opinion in Biotechnology·Jingwen ZhouJian Chen
Aug 3, 2013·Journal of Biotechnology·Asad Ali ShahSeon-Won Kim
Apr 14, 2016·Journal of Agricultural and Food Chemistry·Chengcheng ZhaoYuhong Ren
Apr 22, 2014·Metabolic Engineering·Tamara WriessneggerHarald Pichler
Apr 10, 2013·Progress in Lipid Research·Tamara Wriessnegger, Harald Pichler
Nov 28, 2013·Journal of Analytical Methods in Chemistry·Rama Raju BaadheYalavarthy Prameela Devi
Jul 22, 2014·FEMS Yeast Research·Michael K Jensen, Jay D Keasling
Jun 11, 2016·Current Opinion in Biotechnology·Zhiqing Wang, Patrick C Cirino
Dec 17, 2014·Metabolic Engineering·Codruta IgneaSotirios C Kampranis
Jan 6, 2017·Biotechnology & Genetic Engineering Reviews·Amir Roointan, Mohammad Hossein Morowvat
Dec 30, 2014·Current Opinion in Biotechnology·Anastasia Krivoruchko, Jens Nielsen
Mar 17, 2017·Annual Review of Biochemistry·Jens Nielsen
Apr 11, 2018·Microbial Cell Factories·Liang XiongXin-Qing Zhao
Jun 14, 2018·Natural Product Reports·Benjamin J KotopkaChristina D Smolke
Mar 29, 2014·Biotechnology Journal·Irina Borodina, Jens Nielsen
May 24, 2018·Nature Communications·Bin JiaYing-Jin Yuan
Mar 30, 2019·Biotechnology Journal·Jens Nielsen
Nov 30, 2019·FEMS Yeast Research·Chenxi QiuJin Hou

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.