Lactate formation in Caldicellulosiruptor saccharolyticus is regulated by the energy carriers pyrophosphate and ATP
(2010) In Metabolic Engineering 12. p.282-290- Abstract
- Caldicellulosiruptor saccharolyticus displays superior H(2) yields on a wide range of carbon sources provided that lactate formation is avoided. Nevertheless, a low lactate flux is initiated as the growth rate declined in the transition to the stationary phase, which coincides with a drastic decrease in the glucose consumption and acetate production fluxes. In addition, the decrease in growth rate was accompanied by a sudden increase and then decrease in NADH levels. The V'(MAX) of the lactate dehydrogenase (LDH) doubled when the cells entered the stationary phase. Kinetic analysis revealed that at the metabolic level LDH activity is regulated through (i) competitive inhibition by pyrophosphate (PPi, k(i)=1.7mM) and NAD (k(i)=0.43mM) and... (More)
- Caldicellulosiruptor saccharolyticus displays superior H(2) yields on a wide range of carbon sources provided that lactate formation is avoided. Nevertheless, a low lactate flux is initiated as the growth rate declined in the transition to the stationary phase, which coincides with a drastic decrease in the glucose consumption and acetate production fluxes. In addition, the decrease in growth rate was accompanied by a sudden increase and then decrease in NADH levels. The V'(MAX) of the lactate dehydrogenase (LDH) doubled when the cells entered the stationary phase. Kinetic analysis revealed that at the metabolic level LDH activity is regulated through (i) competitive inhibition by pyrophosphate (PPi, k(i)=1.7mM) and NAD (k(i)=0.43mM) and (ii) allosteric activation by FBP (300%), ATP (160%) and ADP (140%). From these data a MWC-based model was derived. Simulations with this model could explain the observed lactate shift by displaying how the sensitivity of LDH activity to NADH/NAD ratio varied with different PP(i) concentrations. Moreover, the activation of LDH by ATP indicates that C. saccharolyticus uses LDH as a means to adjusts its flux of ATP and NADH production. To our knowledge, this is the first time PPi is observed as an effector of LDH. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1541261
- author
- Willquist, Karin LU and van Niel, Ed LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Metabolic Engineering
- volume
- 12
- pages
- 282 - 290
- publisher
- Elsevier
- external identifiers
-
- wos:000276821400010
- pmid:20060925
- scopus:77950864352
- ISSN
- 1096-7176
- DOI
- 10.1016/j.ymben.2010.01.001
- language
- English
- LU publication?
- yes
- id
- 1f444ea0-43b8-470e-8593-38ea6eff835d (old id 1541261)
- date added to LUP
- 2016-04-01 10:38:08
- date last changed
- 2022-01-26 01:02:08
@article{1f444ea0-43b8-470e-8593-38ea6eff835d, abstract = {{Caldicellulosiruptor saccharolyticus displays superior H(2) yields on a wide range of carbon sources provided that lactate formation is avoided. Nevertheless, a low lactate flux is initiated as the growth rate declined in the transition to the stationary phase, which coincides with a drastic decrease in the glucose consumption and acetate production fluxes. In addition, the decrease in growth rate was accompanied by a sudden increase and then decrease in NADH levels. The V'(MAX) of the lactate dehydrogenase (LDH) doubled when the cells entered the stationary phase. Kinetic analysis revealed that at the metabolic level LDH activity is regulated through (i) competitive inhibition by pyrophosphate (PPi, k(i)=1.7mM) and NAD (k(i)=0.43mM) and (ii) allosteric activation by FBP (300%), ATP (160%) and ADP (140%). From these data a MWC-based model was derived. Simulations with this model could explain the observed lactate shift by displaying how the sensitivity of LDH activity to NADH/NAD ratio varied with different PP(i) concentrations. Moreover, the activation of LDH by ATP indicates that C. saccharolyticus uses LDH as a means to adjusts its flux of ATP and NADH production. To our knowledge, this is the first time PPi is observed as an effector of LDH.}}, author = {{Willquist, Karin and van Niel, Ed}}, issn = {{1096-7176}}, language = {{eng}}, pages = {{282--290}}, publisher = {{Elsevier}}, series = {{Metabolic Engineering}}, title = {{Lactate formation in Caldicellulosiruptor saccharolyticus is regulated by the energy carriers pyrophosphate and ATP}}, url = {{http://dx.doi.org/10.1016/j.ymben.2010.01.001}}, doi = {{10.1016/j.ymben.2010.01.001}}, volume = {{12}}, year = {{2010}}, }