%0 Journal Article %1 Siegel2015Computational %A Siegel, Justin B. %A Smith, Amanda L. %A Poust, Sean %A Wargacki, Adam J. %A Bar-Even, Arren %A Louw, Catherine %A Shen, Betty W. %A Eiben, Christopher B. %A Tran, Huu M. %A Noor, Elad %A Gallaher, Jasmine L. %A Bale, Jacob %A Yoshikuni, Yasuo %A Gelb, Michael H. %A Keasling, Jay D. %A Stoddard, Barry L. %A Lidstrom, Mary E. %A Baker, David %D 2015 %I National Academy of Sciences %J Proceedings of the National Academy of Sciences %K design metabolic-network proteins %N 12 %P 3704--3709 %R 10.1073/pnas.1500545112 %T Computational protein design enables a novel one-carbon assimilation pathway %U http://dx.doi.org/10.1073/pnas.1500545112 %V 112 %X We describe a computationally designed enzyme, formolase (FLS), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence of FLS enables the design of a new carbon fixation pathway, the formolase pathway, consisting of a small number of thermodynamically favorable chemical transformations that convert formate into a three-carbon sugar in central metabolism. The formolase pathway is predicted to use carbon more efficiently and with less backward flux than any naturally occurring one-carbon assimilation pathway. When supplemented with enzymes carrying out the other steps in the pathway, FLS converts formate into dihydroxyacetone phosphate and other central metabolites in vitro. These results demonstrate how modern protein engineering and design tools can facilitate the construction of a completely new biosynthetic pathway.

@article{Siegel2015Computational, abstract = {We describe a computationally designed enzyme, formolase ({FLS}), which catalyzes the carboligation of three one-carbon formaldehyde molecules into one three-carbon dihydroxyacetone molecule. The existence of {FLS} enables the design of a new carbon fixation pathway, the formolase pathway, consisting of a small number of thermodynamically favorable chemical transformations that convert formate into a three-carbon sugar in central metabolism. The formolase pathway is predicted to use carbon more efficiently and with less backward flux than any naturally occurring one-carbon assimilation pathway. When supplemented with enzymes carrying out the other steps in the pathway, {FLS} converts formate into dihydroxyacetone phosphate and other central metabolites in vitro. These results demonstrate how modern protein engineering and design tools can facilitate the construction of a completely new biosynthetic pathway.}, added-at = {2018-12-02T16:09:07.000+0100}, author = {Siegel, Justin B. and Smith, Amanda L. and Poust, Sean and Wargacki, Adam J. and Bar-Even, Arren and Louw, Catherine and Shen, Betty W. and Eiben, Christopher B. and Tran, Huu M. and Noor, Elad and Gallaher, Jasmine L. and Bale, Jacob and Yoshikuni, Yasuo and Gelb, Michael H. and Keasling, Jay D. and Stoddard, Barry L. and Lidstrom, Mary E. and Baker, David}, biburl = {https://www.bibsonomy.org/bibtex/29dca4886e42ecce51479eb237f16ce69/karthikraman}, citeulike-article-id = {13553149}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.1500545112}, citeulike-linkout-1 = {http://www.pnas.org/content/112/12/3704.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/112/12/3704.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/25775555}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=25775555}, day = 24, doi = {10.1073/pnas.1500545112}, interhash = {bdd8f735d4328815dfa084cad1ad484b}, intrahash = {9dca4886e42ecce51479eb237f16ce69}, issn = {1091-6490}, journal = {Proceedings of the National Academy of Sciences}, keywords = {design metabolic-network proteins}, month = mar, number = 12, pages = {3704--3709}, pmid = {25775555}, posted-at = {2015-04-15 12:46:21}, priority = {2}, publisher = {National Academy of Sciences}, timestamp = {2018-12-02T16:09:07.000+0100}, title = {Computational protein design enables a novel one-carbon assimilation pathway}, url = {http://dx.doi.org/10.1073/pnas.1500545112}, volume = 112, year = 2015 }