Design and analysis of synthetic carbon fixation pathways.
Carbon fixation is the process by which CO(2) is incorporated into organic compounds. In modern agriculture in which water, light, and nutrients can be abundant, carbon fixation could become a significant growth-limiting factor. Hence, increasing the fixation rate is of major importance in the road toward sustainability in food and energy production. There have been recent attempts to improve the rate and specificity of Rubisco, the carboxylating enzyme operating in the Calvin-Benson cycle; however, they have achieved only limited success. Nature employs several alternative carbon fixation pathways, which prompted us to ask whether more efficient novel synthetic cycles could be devised. Using the entire repertoire of approximately 5,000 metabolic enzymes known to occur in nature, we computationally identified alternative carbon fixation pathways that combine existing metabolic building blocks from various organisms. We compared the natural and synthetic pathways based on physicochemical criteria that include kinetics, energetics, and topology. Our study suggests that some of the proposed synthetic pathways could have significant quantitative advantages over their natural counterparts, such as the overall kinetic rate. One such cycle, which is predicted to be two to three times faster than the Calvin-Benson cycle, employs the most effective carboxylating enzyme, phosphoenolpyruvate carboxylase, using the core of the naturally evolved C4 cycle. Although implementing such alternative cycles presents daunting challenges related to expression levels, activity, stability, localization, and regulation, we believe our findings suggest exciting avenues of exploration in the grand challenge of enhancing food and renewable fuel production via metabolic engineering and synthetic biology.
Bar-Even
Arren
A
Departments of Plant Sciences and Computer Science and Applied Mathematics, The Weizmann Institute of Science, Rehovot 76100, Israel.
Noor
Elad
E
Lewis
Nathan E
NE
Milo
Ron
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D007700:Kinetics; D009249:NADP / Q000378:metabolism; D010788:Photosynthesis; D013816:Thermodynamics
D009249:NADP; D002244:Carbon; D000255:Adenosine Triphosphate
Appl Biochem Biotechnol. 2002 Spring;98-100:37-48
12018264
Nature. 2004 May 20;429(6989):292-4
15152251
J Theor Biol. 2000 Apr 7;203(3):229-48
10716907
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7246-51
16641091
Science. 2009 Sep 25;325(5948):1642-3
19779184
Biochim Biophys Acta. 2008 Dec;1784(12):1873-98
18801467
BMC Evol Biol. 2007 May 11;7:73
17498284
Eur J Biochem. 1991 Oct 1;201(1):1-21
1915354
Curr Opin Plant Biol. 2002 Feb;5(1):43-8
11788307
Photosynth Res. 2004 Feb;79(2):133-48
16228388
Plant Physiol. 2005 May;138(1):451-60
15863701
New Phytol. 2003 Feb;157(2):175-198
33873640
Chem Rev. 2003 Jun;103(6):2333-46
12797832
Proc Natl Acad Sci U S A. 1966 Apr;55(4):928-34
5219700
J Bacteriol. 2006 Dec;188(24):8551-9
17041055
Bull Math Biol. 2001 Jan;63(1):21-55
11146883
J Biol Chem. 2002 Jun 7;277(23):20277-83
11929869
Curr Opin Plant Biol. 2004 Jun;7(3):247-53
15134744
Nat Methods. 2009 Aug;6(8):589-92
19597503
Plant Cell Environ. 2009 Apr;32(4):417-27
19183297
J Exp Bot. 2005 Jan;56(411):435-47
15642715
Biochemistry. 2004 Jul 6;43(26):8281-9
15222740
J Exp Bot. 2002 Apr;53(369):609-20
11886880
Nat Biotechnol. 2007 May;25(5):593-9
17435746
Plant Physiol. 1987 Jul;84(3):959-63
16665551
Biochim Biophys Acta. 1965 Feb 15;97:202-13
14292829
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7851-6
18511565
J Bacteriol. 2002 May;184(9):2404-10
11948153
J Biol Chem. 2009 Feb 27;284(9):5457-61
18940807
Mitochondrion. 2008 Jan;8(1):87-99
18024239
Trends Biotechnol. 2004 Aug;22(8):400-5
15283984
Nucleic Acids Res. 2000 Jan 1;28(1):27-30
10592173
J Theor Biol. 2001 Feb;208(3):361-82
11207096
Mol Microbiol. 2006 Feb;59(4):1073-82
16430685
Bacteriol Rev. 1977 Mar;41(1):100-80
860983
Plant Cell Environ. 2006 Mar;29(3):331-9
17080589
J Theor Biol. 1991 Nov 21;153(2):195-203
1787736
Science. 2007 Dec 14;318(5857):1782-6
18079405
J Biol Chem. 1985 Oct 25;260(24):13181-9
4055736
Plant Cell Environ. 2006 Mar;29(3):315-30
17080588
Trends Biotechnol. 1999 Feb;17(2):53-60
10087604
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3475-80
20142476
J Theor Biol. 1985 Nov 21;117(2):251-63
4079448
Genome Res. 2004 Nov;14(11):2367-76
15520298