Quantitative Analysis of the High Temperature-induced Glycolytic Flux Increase in Saccharomyces cerevisiae Reveals Dominant Metabolic Regulation

A major challenge in systems biology lies in the integration of processes occurring at different levels, such as transcription, translation, and metabolism, to understand the functioning of a living cell in its environment. We studied the high temperature-induced glycolytic flux increase in Saccharomyces cerevisiae and investigated the regulatory mechanisms underlying this increase. We used glucose-limited chemostat cultures to separate regulatory effects of temperature from effects on at temperature in a glycolytic a from to a We flux from to We the of temperature effects on the and in the to the flux this flux We the of temperature on as a separate and this the flux the of the temperature on the and a to the glycolytic flux in flux in the of the and A major challenge in systems biology lies in the integration of processes occurring at different levels, such as transcription, translation, and metabolism, to understand the functioning of a living cell in its environment. We studied the high temperature-induced glycolytic flux increase in Saccharomyces cerevisiae and investigated the regulatory mechanisms underlying this increase. We used glucose-limited chemostat cultures to separate regulatory effects of temperature from effects on at temperature in a glycolytic a from to a We flux from to We the of temperature effects on the and in the to the flux this flux We the of temperature on as a separate and this the flux the of the temperature on the and a to the glycolytic flux in flux in the of the and to and to in to in temperature to the and of and temperature and as as and temperature in the on the of to to high temperature such as and the of of a of in of in the of the to in of and as as in of of a on the on the mechanisms a the to and processes on the of a temperature studied to the of the to the effects of temperature temperature a on the of temperature of the on the of to this increase in temperature in in increase in this the effects of in the of the at as transcription, and flux such as increase in in studied the of temperature on the and of Saccharomyces cerevisiae at the and to this investigated the of temperature on as a separate this the the increase in glycolytic flux at temperature at the of and temperature effects and cerevisiae in temperature to and of a of at used on in a of at a of in in at and used chemostat the as used in to the to and temperature of the chemostat a and a temperature and temperature the chemostat at the and and in of on and of and in a in a and on and in the of the and a of and of in of of and high on a as to and of a to the at to to in in a at a of to the the of at and of the to the of in a in at of and to of flux a to from the cell the of the and of used in the a and used to as and as the the of of and of to of and in the at and at to the and to and to the of to of the of from at chemostat cultures a and the as to and to in and the a the of at on of the A used to at to of the the to the on a to a and the the in and and and and of the used to the to in the of temperature on cerevisiae in and at in the of in the temperature increase of temperature a at the temperature to a increase of temperature to a separate the of temperature on glycolytic flux from the of in on metabolism, used in the to We used a of to the of temperature on to in the and in the cultures the the temperature of and of and the in at flux in the of the in the of the a metabolism, We used the of and to the the of at and the in and the at the to We a flux glycolytic in cultures at and this increase on of chemostat cultures at in the of of temperature on and of temperature on flux flux flux flux and flux of the and We the in this the flux to the the in the of and in the of the glycolytic at temperature a on the of the on the of on in the of the flux in the of such as and the in flux of the of the of temperature on of glycolytic the temperature of the in at and in cell from chemostat at this to the of temperature on from of the of the cell to the temperature increase. in the of the in of temperature on in cell from at from to of the the increase in in cell from at the of temperature from to cell the and a in at the the of to the of from at at in of temperature on of cell from in different from on the of cell from and of at of cerevisiae in glucose-limited at and temperature temperature temperature temperature temperature temperature temperature temperature temperature temperature from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a in a of the of temperature on and in a the on the of and a the of the of from at the of and in from to the at at different in the of and different the of from at a the temperature-induced flux increase a temperature in the of glycolytic at of in the of the the of and the of processes to the increase in glycolytic used of the at a the flux the in at the its the and of the and and the in in the the of and the of and in this the of the of of the temperature as in in A a the of the the and the the of and the the We a of at to the flux as in the of the flux of in the of of temperature the and the the of in the of the the of in to the in the at different effects on the of the in the and from the from in the at to the from cultures at different at from the of temperature on from of the on the different different temperature We the at to of from a different temperature this the and from from at its from the used the to in a flux in to increase in of the in flux increase of the of in at and the flux this of the this as as of the of flux as in of to flux and in the of and and temperature of to the flux increase. in temperature to the flux increase. the increase in flux glycolytic in to a temperature increase from to in of flux temperature flux in cultures the of the a of a flux of and used this flux this flux of this flux in cultures the of the a of a flux of and used this flux this flux of this in a and of the of the in to the temperature-induced flux glycolytic in from chemostat at and the glycolytic in at in at the this in in a in the of different to in and studied and of We the of and in and and of the this and the of this to the in flux increase this in the flux increase a temperature in the of the environment. the of glycolytic to the in and the of glycolytic of and from to in at at of and and of the of in cultures at of in the of and a of the in to the flux of the of in increase in the of the a of a of a high flux at the of its the the of the and metabolism, a of at in the of high of to its the of the and the of glycolytic the of cultures at cultures at in the of of at and the of the to the glycolytic flux this to the increase of the at of chemostat cultures at and of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a in a processes in living on a studied cerevisiae its systems increase in studied the of in to and of in to of the in to the of the temperature effects on the effects of in and of the cell to the flux the glycolytic We and a as a separate used the to the mechanisms the glycolytic flux increase a temperature We a of temperature on the to the flux increase of the flux increase in the of the of the of temperature on glycolytic flux the from a to a metabolism, the on the of at We to this the at a in a to cultures and a in to high of the of the of a temperature of of this the in and at to the cell and the flux the at the of of flux used We a separate regulatory glycolytic at and in cell from chemostat cultures at the of temperature on from to a the of high temperature on the of glycolytic temperature of as the a of the of the of a as a of the temperature a of this to in on the of the of We the glycolytic in to from a on at a temperature the temperature of to the in and to the of at the temperature of the to of at high a of temperature on of the of of of the We in at a and We the the of a different of the effects in the in and different in a the the of and of temperature from at different the of to temperature in and of of the and to We in glycolytic in a the high flux at this of flux different in the different to in this the of the of in the from a to a in the to the in of in glycolytic the flux the of temperature and the temperature-induced flux increase in of the the the high glycolytic flux at high glycolytic flux flux and the at the at at the this increase in the at the temperature glycolytic flux in a of to glycolytic flux at in in cerevisiae at in this to a high flux its a as as a regulatory as temperature We a high flux in the of a the of the of and a of the of the such regulatory effects in temperature effects on of effects at a temperature increase to a increase in glycolytic flux at increase in the of temperature as flux increase of a temperature of a of the in flux at glycolytic the of to and to in to in temperature to the and of and temperature and as as and temperature in the on the of to to high temperature such as and the of of a of in of in the of the to in of and as as in of of a on the on the mechanisms a the to and processes on the of a temperature studied to the of the to the effects of temperature temperature a on the of temperature of the on the of to this increase in temperature in in increase in this the effects of in the of the at as transcription, and flux such as increase in in studied the of temperature on the and of Saccharomyces cerevisiae at the and to this investigated the of temperature on as a separate this the the increase in glycolytic flux at temperature at the of and temperature effects and cerevisiae in temperature to and of a of at used on in a of at a of in in at and used chemostat the as used in to the to and temperature of the chemostat a and a temperature and temperature the chemostat at the and and in of on and of and in a in a and on and in the of the and a of and of in of of and high on a as to and of a to the at to to in in a at a of to the the of at and of the to the of in a in at of and to of flux a to from the cell the of the and of used in the a and used to as and as the the of of and of to of and in the at and at to the and to and to the of to of the of from at chemostat cultures a and the as to and to in and the a the of at on of the A used to at to of the the to the on a to a and the the in and and and and of the used to the and cerevisiae in temperature to and of a of at used on in a of at a of in in at and used chemostat the as used in to the to and temperature of the chemostat a and a temperature and temperature the chemostat at the and and in of on and of and in a in a and on and in the of the and a of and of in of of and high on a as to and of a to the at to to in in a at a of to the the of at and of the to the of in a in at of and to of flux a to from the cell the of the and of used in the a and used to as and as the the of of and of to of and in the at and at to the and to and to the of to of the of from at chemostat cultures a and the as to and to in and the a the of at on of the A used to at to of the the to the on a to a and the the in and and and and of the used to the to in the of temperature on cerevisiae in and at in the of in the temperature increase of temperature a at the temperature to a increase of temperature to a separate the of temperature on glycolytic flux from the of in on metabolism, used in the to We used a of to the of temperature on to in the and in the cultures the the temperature of and of and the in at flux in the of the in the of the a metabolism, We used the of and to the the of at and the in and the at the to We a flux glycolytic in cultures at and this increase of the and We the in this the flux to the the in the of and in the of the glycolytic at temperature a on the of the on the of on in the of the flux in the of such as and the in flux of the of the of temperature on of glycolytic the temperature of the in at and in cell from chemostat at this to the of temperature on from of the of the cell to the temperature increase. in the of the in of temperature on in cell from at from to of the the increase in in cell from at the of temperature from to cell the and a in at the the of to the of from at at in of temperature on of cell from in different from on the of cell from and of at of cerevisiae in glucose-limited at and temperature temperature temperature temperature temperature temperature temperature temperature temperature temperature from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a from a in a of the of temperature on and in a the on the of and a the of the of from at the of and in from to the at at different in the of and different the of from at a the temperature-induced flux increase a temperature in the of glycolytic at of in the of the the of and the of processes to the increase in glycolytic used of the at a the flux the in at the its the and of the and and the in in the the of and the of and in this the of the of of the temperature as in in A a the of the the and the the of and the the We a of at to the flux as in the of the flux of in the of of temperature the and the the of in the of the the of in to the in the at different effects on the of the in the and from the from in the at to the from cultures at different at from the of temperature on from of the on the different different temperature We the at to of from a different temperature this the and from from at its from the used the to in a flux in to increase in of the in flux increase of the of in at and the flux this of the this as as of the of flux as in of to flux and in the of and and temperature of to the flux increase. in temperature to the flux increase. the increase in flux glycolytic in to a temperature increase from to in of flux temperature flux in cultures the of the a of a flux of and used this flux this flux of this flux in cultures the of the a of a flux of and used this flux this flux of this in a and of the of the in to the temperature-induced flux glycolytic in from chemostat at and the glycolytic in at in at the this in in a in the of different to in and studied and of We the of and in and and of the this and the of this to the in flux increase this in the flux increase a temperature in the of the environment. the of glycolytic to the in and the of glycolytic of and from to in at at of and and of the of in cultures at of in the of and a of the in to the flux of the of in increase in the of the a of a of a high flux at the of its the the of the and metabolism, a of at in the of high of to its the of the and the of glycolytic the of cultures at cultures at in the of of at and the of the to the glycolytic flux this to the increase of the at of chemostat cultures at and of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a of the as a in a to in the of temperature on cerevisiae in and at in the of in the temperature increase of temperature a at the temperature to a increase of temperature to a separate the of temperature on glycolytic flux from the of in on metabolism, used in the to We used a of to the of temperature on to in the and in the cultures the the temperature of and of and the in at flux in the of the in the of the a metabolism, We used the of and to the the of at and the in and the at the to We a flux glycolytic in cultures at and this increase of the glycolytic at temperature a on the of the on the of on in the of the flux in the of such as and the in flux of the of the of temperature on of glycolytic the temperature of the in at and in cell from chemostat at this to the of temperature on from of the of the cell to the temperature increase. in the of the in of temperature on in cell from at from to of the the increase in in cell from at the of temperature from to cell the and a in at the the of to the of from at at in of temperature on of cell from in different from on the of cell from and of at the on the of and a the of the of from at the of and in from to the at at different in the of and different the of from at a the temperature-induced flux increase a temperature in the of glycolytic at increase. of in the of the the of and the of processes to the increase in glycolytic used of the at a the flux the in at the its the and of the and and the in in the the of and the of and in this the of the of of the temperature as in in A a the of the the and the the of and the the We a of at to the flux as in the of the flux of in the of of temperature the and the the of in the of the the of in to the in the at different effects on the of the in the and We from the from in the at to the from cultures at different at from the of temperature on from of the on the different different temperature We the at to of from a different temperature this the and from from at its from the We used the to in a flux in to increase in of the in flux increase of the of in at and the flux this of the this as as of the of flux as in of to flux and in the of and and temperature of to the flux increase. in temperature to the flux increase. the increase in flux glycolytic in to a temperature increase from to in environment. and of the of the in to the temperature-induced flux glycolytic in from chemostat at and the glycolytic in at in at the this in in a in the of different to in and studied and of We the of and in and and of the this and the of this to the in flux increase this in the flux increase a temperature in the of the environment. the of glycolytic to the in and the of glycolytic of and from to in at at of and and of the of in cultures at of in the of and a of the in to the flux of the of in increase in the of the a of a of a high flux at the of its the the of the and metabolism, a of at in the of high of to its the of the and the of glycolytic the of cultures at cultures at in the of of at and the of the to the glycolytic flux this to the increase of the at processes in living on a studied cerevisiae its systems increase in studied the of in to and of in to of the in to the of the temperature effects on the effects of in and of the cell to the flux the glycolytic We and a as a separate used the to the mechanisms the glycolytic flux increase a temperature We a of temperature on the to the flux increase of the flux increase in the of the of the of temperature on glycolytic flux the from a to a metabolism, the on the of at We to this the at a in a to cultures and a in to high of the of the of a temperature of of this the in and at to the cell and the flux the at the of of flux used We a separate regulatory glycolytic at and in cell from chemostat cultures at the of temperature on from to a the of high temperature on the of glycolytic temperature of as the a of the of the of a as a of the temperature a of this to in on the of the of We the glycolytic in to from a on at a temperature the temperature of to the in and to the of at the temperature of the to of at high a of temperature on of the of of of the We in at a and We the the of a different of the effects in the in and different in a the the of and of temperature from at different the of to temperature in and of of the and to We in glycolytic in a the high flux at this of flux different in the different to in this the of the of in the from a to a in the to the in of in glycolytic the flux the of temperature and the temperature-induced flux increase in of the the the high glycolytic flux at high glycolytic flux flux and the at the at at the this increase in the at the temperature glycolytic flux in a of to glycolytic flux at in in cerevisiae at in this to a high flux its a as as a regulatory as temperature We a high flux in the of a the of the of and a of the of the such regulatory effects in temperature effects on of effects at a temperature increase to a increase in glycolytic flux at increase in the of temperature as flux increase of a temperature of a of the in flux at glycolytic the of processes in living on a studied cerevisiae its systems increase in studied the of in to and of in to of the in to the of the temperature effects on the effects of in and of the cell to the flux the glycolytic We and a as a separate used the to the mechanisms the glycolytic flux increase a temperature We a of temperature on the to the flux increase of the flux increase in the of the of the of temperature on glycolytic flux the from a to a metabolism, the on the of at We to this the at a in a to cultures and a in to high of the of the of a temperature of of this the in and at to the cell and the flux the at the of of flux used We a separate regulatory glycolytic at and in cell from chemostat cultures at the of temperature on from to a the of high temperature on the of glycolytic temperature of as the a of the of the of a as a of the temperature a of this to in on the of the of We the glycolytic in to from a on at a temperature the temperature of to the in and to the of at the temperature of the to of at high a of temperature on of the of of of the We in at a and We the the of a different of the effects in the in and different in a the the of and of temperature from at different the of to temperature in and of of the and to We in glycolytic in a the high flux at this of flux different in the different to in this the of the of in the from a to a in the to the in of in glycolytic the flux the of temperature and the temperature-induced flux increase in of the the the high glycolytic flux at high glycolytic flux flux and the at the at at the this increase in the at the temperature glycolytic flux in a of to glycolytic flux at in in cerevisiae at in this to a high flux its a as as a regulatory as temperature We a high flux in the of a the of the of and a of the of the such regulatory effects in temperature effects on of effects at a temperature increase to a increase in glycolytic flux at increase in the of temperature as flux increase of a temperature of a of the in flux at glycolytic the of We