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Title: Reaction kinetic analysis of the 3-hydroxypropionate/4-hydroxybutyrate CO 2 fixation cycle in extremely thermoacidophilic archaea

Here, the 3-hydroxypropionate/4-hydroxybutyrate (3HP/4HB) cycle fixes CO 2 in extremely thermoacidophilic archaea and holds promise for metabolic engineering because of its thermostability and potentially rapid pathway kinetics. A reaction kinetics model was developed to examine the biological and biotechnological attributes of the 3HP/4HB cycle as it operates in Metallosphaera sedula, based on previous information as well as on kinetic parameters determined here for recombinant versions of five of the cycle enzymes (malonyl-CoA/succinyl-CoA reductase, 3-hydroxypropionyl-CoA synthetase, 3-hydroxypropionyl-CoA dehydratase, acryloyl-CoA reductase, and succinic semialdehyde reductase). The model correctly predicted previously observed features of the cycle: the 35%–65% split of carbon flux through the acetyl-CoA and succinate branches, the high abundance and relative ratio of acetyl-CoA/propionyl-CoA carboxylase (ACC) and MCR, and the significance of ACC and hydroxybutyryl-CoA synthetase (HBCS) as regulated control points for the cycle. The model was then used to assess metabolic engineering strategies for incorporating CO 2 into chemical intermediates and products of biotechnological importance: acetyl-CoA, succinate, and 3-hydroxyproprionate.
 [1] ;  [2] ;  [1] ;  [3] ;  [4] ;  [4] ;  [4] ;  [4] ;  [5]
  1. North Carolina State Univ., Raleigh, NC (United States); Novozymes North America Inc., Franklinton, NC (United States)
  2. North Carolina State Univ., Raleigh, NC (United States); Chinese Academy of Sciences, Beijing (China)
  3. North Carolina State Univ., Raleigh, NC (United States); Xiamen Univ., Fujan Province (China)
  4. Univ. of Georgia, Athens, GA (United States)
  5. North Carolina State Univ., Raleigh, NC (United States)
Publication Date:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Metabolic Engineering
Additional Journal Information:
Journal Volume: 38; Journal Issue: C; Journal ID: ISSN 1096-7176
Research Org:
North Carolina State Univ., Raleigh, NC (United States)
Sponsoring Org:
USDOE Advanced Research Projects Agency - Energy (ARPA-E)
Country of Publication:
United States
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; CO2 fixation; 3-hydroxypropionate; 4-hydroxybutyrate; Metallosphaera sedula
OSTI Identifier:
Alternate Identifier(s):
OSTI ID: 1410825