title: Genome-Scale Metabolic Model for the Green Alga Chlorella vulgaris UTEX 395 Accurately Predicts Phenotypes under Autotrophic, Heterotrophic, and Mixotrophic Growth Conditions.
abstract: The green microalga Chlorella vulgaris has been widely recognized as a promising candidate for biofuel production due to its ability to store high lipid content and its natural metabolic versatility. Compartmentalized genome-scale metabolic models constructed from genome sequences enable quantitative insight into the transport and metabolism of compounds within a target organism. These metabolic models have long been utilized to generate optimized design strategies for an improved production process. Here, we describe the reconstruction, validation, and application of a genome-scale metabolic model for C. vulgaris UTEX 395, iCZ843. The reconstruction represents the most comprehensive model for any eukaryotic photosynthetic organism to date, based on the genome size and number of genes in the reconstruction. The highly curated model accurately predicts phenotypes under photoautotrophic, heterotrophic, and mixotrophic conditions. The model was validated against experimental data and lays the foundation for model-driven strain design and medium alteration to improve yield. Calculated flux distributions under different trophic conditions show that a number of key pathways are affected by nitrogen starvation conditions, including central carbon metabolism and amino acid, nucleotide, and pigment biosynthetic pathways. Furthermore, model prediction of growth rates under various medium compositions and subsequent experimental validation showed an increased growth rate with the addition of tryptophan and methionine.
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Cristal
authors.initials: C
authors.lastname: Zuñiga
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Chien-Ting
authors.initials: CT
authors.lastname: Li
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Tyler
authors.identifier: 0000-0003-3111-3510
authors.initials: T
authors.lastname: Huelsman
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Jennifer
authors.identifier: 0000-0001-8491-9337
authors.initials: J
authors.lastname: Levering
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Zielinski
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Brian O
authors.identifier: 0000-0002-7418-4813
authors.initials: BO
authors.lastname: McConnell
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Christopher P
authors.identifier: 0000-0003-1007-417X
authors.initials: CP
authors.lastname: Long
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Eric P
authors.identifier: 0000-0002-5709-914X
authors.initials: EP
authors.lastname: Knoshaug
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Michael T
authors.initials: MT
authors.lastname: Guarnieri
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Maciek R
authors.initials: MR
authors.lastname: Antoniewicz
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.).
authors.forename: Michael J
authors.identifier: 0000-0002-6336-4659
authors.initials: MJ
authors.lastname: Betenbaugh
authors.affiliation: Department of Bioengineering, University of California, San Diego, La Jolla, California 92093-0412 (C.Z., T.H., J.L., D.C.Z., K.Z.);Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218 (C.-T.L., M.J.B.);Department of Chemical and Biomolecular Engineering, Metabolic Engineering and Systems Biology Laboratory, University of Delaware, Newark, Delaware 19716 (B.O.M., C.P.L., M.R.A.); andNational Bioenergy Center, National Renewable Energy Laboratory, Golden, Colorado 80401 (E.P.K., M.T.G.) kzengler@ucsd.edu.
authors.forename: Karsten
authors.initials: K
authors.lastname: Zengler
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D052818:Autotrophic Processes; D018533:Biomass; D002244:Carbon / Q000378:metabolism; D048408:Chlorella vulgaris / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D018745:Genome, Plant / Q000235:genetics; D052836:Heterotrophic Processes; D053858:Metabolic Networks and Pathways / Q000235:genetics; D058086:Microalgae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D008954:Models, Biological; D010860:Pigments, Biological / Q000378:metabolism
chemical_list: D000596:Amino Acids; D010860:Pigments, Biological; D002244:Carbon