scholarly journals A Physiological Characterization in Controlled Bioreactors Reveals a Novel Survival Strategy for Debaryomyces hansenii at High Salinity and Confirms its Halophilic Behavior

Author(s):  
Clara Navarrete ◽  
August T. Frost ◽  
Laura Ramos-Moreno ◽  
Mette R. Krum ◽  
José L. Martínez

AbstractDebaryomyces hansenii is traditionally described as a halotolerant non-conventional yeast, being the model organism for the study of osmo- and salt tolerance mechanisms in eukaryotic systems for the past 30 years.However, unravelling of D. hansenii’s biotechnological potential has always been difficult due to the persistent limitations in the availability of efficient molecular tools described for this yeast. Additionally, there is a lack of consensus and contradictory information along the recent years that limits a comprehensive understanding of its central carbon metabolism, mainly due to a lack of physiological studies in controlled and monitored environments. Moreover, there is controversy about the diversity in the culture conditions (media composition, temperature and pH among others) used by different groups, which makes it complicated when trying to get significant conclusions and behavioural patterns.In this work, we present for the first time a physiological characterization of D. hansenii in batch cultivations using highly instrumented and controlled lab-scale bioreactors. Our findings contribute to a more complete picture of the central carbon metabolism and the external pH influence on the yeast ability to tolerate high Na+ and K+ concentrations. Finally, the controversial halophilic/halotolerant character of this yeast is further clarified.

2011 ◽  
Vol 287 (6) ◽  
pp. 4260-4274 ◽  
Author(s):  
Tobias Härtel ◽  
Eva Eylert ◽  
Christian Schulz ◽  
Lothar Petruschka ◽  
Philipp Gierok ◽  
...  

2016 ◽  
Vol 37 ◽  
pp. 102-113 ◽  
Author(s):  
Christopher P. Long ◽  
Jacqueline E. Gonzalez ◽  
Nicholas R. Sandoval ◽  
Maciek R. Antoniewicz

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Volkan I Sayin ◽  
Sarah E LeBoeuf ◽  
Simranjit X Singh ◽  
Shawn M Davidson ◽  
Douglas Biancur ◽  
...  

During tumorigenesis, the high metabolic demand of cancer cells results in increased production of reactive oxygen species. To maintain oxidative homeostasis, tumor cells increase their antioxidant production through hyperactivation of the NRF2 pathway, which promotes tumor cell growth. Despite the extensive characterization of NRF2-driven metabolic rewiring, little is known about the metabolic liabilities generated by this reprogramming. Here, we show that activation of NRF2, in either mouse or human cancer cells, leads to increased dependency on exogenous glutamine through increased consumption of glutamate for glutathione synthesis and glutamate secretion by xc- antiporter system. Together, this limits glutamate availability for the tricarboxylic acid cycle and other biosynthetic reactions creating a metabolic bottleneck. Cancers with genetic or pharmacological activation of the NRF2 antioxidant pathway have a metabolic imbalance between supporting increased antioxidant capacity over central carbon metabolism, which can be therapeutically exploited.


2004 ◽  
Vol 186 (13) ◽  
pp. 4185-4191 ◽  
Author(s):  
Naeem Rashid ◽  
Hiroyuki Imanaka ◽  
Toshiaki Fukui ◽  
Haruyuki Atomi ◽  
Tadayuki Imanaka

ABSTRACT Numerous bacteria and mammalian cells harbor two enzymes, phosphopentomutase (PPM) and 2-deoxyribose 5-phosphate aldolase (DERA), involved in the interconversion between nucleosides and central carbon metabolism. In this study, we have examined the presence of this metabolic link in the hyperthermophilic archaeon, Thermococcus kodakaraensis KOD1. A search of the genome sequence of this strain revealed the presence of a closely related orthologue (TK2104) of bacterial DERA genes while no orthologue related to previously characterized PPM genes could be detected. Expression, purification, and characterization of the TK2104 protein product revealed that this gene actually encoded a DERA, catalyzing the reaction through a class I aldolase mechanism. As PPM activity was detected in T. kodakaraensis cells, we partially purified the protein to examine its N-terminal amino acid sequence. The sequence corresponded to a gene (TK1777) similar to phosphomannomutases within COG1109 but not COG1015, which includes all previously identified PPMs. Heterologous gene expression of TK1777 and characterization of the purified recombinant protein clearly revealed that the gene indeed encoded a PPM. Both enzyme activities could be observed in T. kodakaraensis cells under glycolytic and gluconeogenic growth conditions, whereas the addition of ribose, 2-deoxyribose, and 2′-deoxynucleosides in the medium did not lead to a significant induction of these activities. Our results clearly indicate the presence of a metabolic link between pentoses and central carbon metabolism in T. kodakaraensis, providing an alternative route for pentose biosynthesis through the functions of DERA and a structurally novel PPM.


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