Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase

Choi, Jin Wook; Silva, Nancy A. Da

doi:10.1016/j.jbiotec.2014.07.430

Cited by 82 publications

(57 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1). Fatty acids are synthesized with acetyl-CoA and malonyl-CoA starters [5,6,30]. Leman reported that a relatively high carbon-nitrogen ratio would improve fatty acids synthesis from acetyl-CoA and malonyl-CoA [17].…”

Section: Discussionmentioning

confidence: 99%

Mutagenesis breeding of high echinocandin B producing strain and further titer improvement with culture medium optimization

Zou

Zhong

Xia

et al. 2015

Bioprocess Biosyst Eng

View full text Add to dashboard Cite

A combination of microbial strain improvement and statistical optimization is investigated to maximize echinocandin B (ECB) production from Aspergillus nidulans ZJB-0817. A classical sequential mutagenesis was studied first by using physical (ultraviolet irradiation at 254 nm) and chemical mutagens (lithium chloride and sodium nitrite). Mutant strain ULN-59 exhibited 2.1-fold increase in ECB production to 1583.1 ± 40.9 mg/L when compared with the parent strain (750.8 ± 32.0 mg/L). This is the first report where mutagenesis is applied in Aspergillus to improve ECB production. Further, fractional factorial design and central composite design were adopted to optimize the culture medium for increasing ECB production by the mutant ULN-59. Results indicated that four culture media including peptone, K2HPO4, mannitol and L-ornithine had significant effects on ECB production. The optimized medium provided another 1.4-fold increase in final ECB concentration to 2285.6 ± 35.6 mg/L compared to the original medium. The results of this study indicated the combined application of a classical mutation and medium optimization can improve effectively ECB production from A. nidulans and could be a promising tool to improve other secondary metabolites production by fungal strains.

show abstract

Section: Discussionmentioning

confidence: 99%

Mutagenesis breeding of high echinocandin B producing strain and further titer improvement with culture medium optimization

Zou

Zhong

Xia

et al. 2015

Bioprocess Biosyst Eng

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

“…Whereas Ac-CoA is abundant in Saccharomyces cerevisiae (S. ceverisiae), the biosynthetic product from the carboxylation of Ac-CoA, Mal-CoA, is limited under normal conditions. Several initiatives have been pursued to increase the Mal-CoA pool size, thereby increasing the production of polyketides, making the Mal-CoA/Ac-CoA ratio an important parameter to monitor [6,7].To obtain the true metabolic image of the cell, instantaneous quenching of the enzyme activities is required. The quenching is often done by rapid changes in temperature or pH and is followed by extraction of the intracellular metabolites [8][9][10][11].…”

mentioning

confidence: 99%

See 1 more Smart Citation

Quantifying intracellular metabolites in yeast using a matrix with minimal interference from naturally occurring analytes

Magdenoska

Knudsen

Svenssen

et al. 2015

Analytical Biochemistry

View full text Add to dashboard Cite

“…In yeast, lack of Snf1 leads to inability to utilize carbon sources that are less preferred than glucose, including sucrose, galactose, maltose, and starch (9)(10)(11). Genetic manipulation of Snf1 and/or its targets has been a useful strategy for achieving various practical goals in yeast biotechnology, such as improved maltose utilization (12), galactose utilization and ethanol production (13), fatty acid production (14,15), and biomass yields (16).…”

mentioning

confidence: 99%

Springing into Action: Reg2 Negatively Regulates Snf1 Protein Kinase and Facilitates Recovery from Prolonged Glucose Starvation in Saccharomyces cerevisiae

Maziarz

Shevade

Barrett

et al. 2016

Appl Environ Microbiol

View full text Add to dashboard Cite

Glucose is the preferred carbon source for the yeast Saccharomyces cerevisiae. Glucose limitation activates Snf1 protein kinase, a key regulator of energy homeostasis that promotes utilization of alternative carbon sources and enforces energy conservation. Snf1 activation requires phosphorylation of its T-loop threonine (Thr210) by upstream kinases. When glucose is abundant, Snf1 is inhibited by Thr210 dephosphorylation. This involves the function of the type 1 protein phosphatase Glc7, which is targeted to Snf1 by a regulatory subunit, Reg1. The reg1 mutation causes increased Snf1 activity and mimics various aspects of glucose limitation, including slower growth. Reg2 is another Glc7 regulatory subunit encoded by a paralogous gene, REG2. Previous evidence indicated that the reg2 mutation exacerbates the Snf1-dependent slow-growth phenotype caused by reg1, suggesting a link between Reg2 and Snf1. Here, we explore this link in more detail and present evidence that Reg2 contributes to Snf1 Thr210 dephosphorylation. Consistent with this role, Reg2 interacts with wild-type Snf1 but not with nonphosphorylatable Snf1-T210A. Reg2 accumulation increases in a Snf1-dependent manner during prolonged glucose deprivation, and glucose-starved cells lacking Reg2 exhibit delayed Snf1 Thr210 dephosphorylation and slower growth recovery upon glucose replenishment. Accordingly, cells lacking Reg2 are outcompeted by wild-type cells in the course of several glucose starvation/replenishment cycles. Collectively, our results support a model in which Reg2-Glc7 contributes to the negative control of Snf1 in response to glucose refeeding after prolonged starvation. The competitive growth advantage provided by Reg2 underscores the evolutionary significance of this paralog for S. cerevisiae. IMPORTANCEThe ability of microorganisms to respond to stress is essential for their survival. However, rapid recovery from stress could be equally crucial in competitive environments. Therefore, a wise stress response program should prepare cells for quick recovery upon reexposure to favorable conditions. Glucose is the preferred carbon source for the yeast S. cerevisiae. Glucose depletion activates the stress response protein kinase Snf1, which functions to limit energy-consuming processes, such as growth. We show that prolonged glucose deprivation also leads to Snf1-dependent accumulation of Reg2 and that this protein helps to inhibit Snf1 and to accelerate growth recovery upon glucose replenishment. Cells lacking Reg2 are readily outcompeted by wild-type cells during glucose depletion/replenishment cycles. Thus, while prolonged glucose deprivation might seem to put yeast cells "on their knees," concomitant accumulation of Reg2 helps configure the cells into a "sprinter's crouch start position" to spring into action once glucose becomes available. Glucose is a preferred source of carbon and energy for a wide variety of microorganisms. Although the yeast Saccharomyces cerevisiae can exist in many different environments, it is particularly know...

show abstract

Improving polyketide and fatty acid synthesis by engineering of the yeast acetyl-CoA carboxylase

Cited by 82 publications

References 27 publications

Mutagenesis breeding of high echinocandin B producing strain and further titer improvement with culture medium optimization

Mutagenesis breeding of high echinocandin B producing strain and further titer improvement with culture medium optimization

Quantifying intracellular metabolites in yeast using a matrix with minimal interference from naturally occurring analytes

Springing into Action: Reg2 Negatively Regulates Snf1 Protein Kinase and Facilitates Recovery from Prolonged Glucose Starvation in Saccharomyces cerevisiae

Contact Info

Product

Resources

About