TY - JOUR
T1 - Assembly of Macromolecular Complexes in the Whole-Cell Model of a Minimal Cell
AU - Fu, Enguang
AU - Thornburg, Zane R.
AU - Brier, Troy A.
AU - Wei, Rong
AU - Yuan, Bo
AU - Gilbert, Benjamin R.
AU - Wang, Shulei
AU - Luthey-Schulten, Zaida
N1 - E.F. and Z.L-S. are partially supported by NSF MCB-2221237 and the NSF Science and Technology Center for Quantitative Cell Biology (NSF DBI-2243257). T.B. and B.G. are partially supported by NSF MCB-2221237. S.W., B.Y., and R.W. are partially supported by NSF DMS-2515171 and the NSF Science and Technology Center for Quantitative Cell Biology (NSF DBI-2243257). Z.R.T.: Research reported in this publication was supported by the Cancer Center at Illinois─Beckman Institute Postdoctoral Fellows Program, sponsored by the Cancer Center at Illinois and the Beckman Institute for Advanced Science and Technology, University of Illinois Urbana–Champaign. The content is solely the responsibility of the authors and does not necessarily represent the official views of the program sponsors.
PY - 2026/1/8
Y1 - 2026/1/8
N2 - Macromolecular complexes in the genetically minimized bacterium, JCVI-syn3A, support gene expression (RNA polymerase, ribosome, degradosome), metabolism (ABC transporters, ATP synthase), and chromosome dynamics. In this work, we further incorporate the assembly of 21 unique macromolecular complexes into the existing whole-cell kinetic model of Syn3A. The synthesis and translocation of protein subunits in membrane complexes occur through distinct pathways. A range of 2D association rates for membrane complexes were considered to guarantee a high yield of assembly, given the existing time scales of gene expression. By alleviation of the undesired kinetically trapped intermediates in ATP synthase assembly, the efficiency was improved. The assembly of RNA polymerase, ribosome, and degradosome influences the speed and efficiency of protein synthesis. Collectively, this model predicted time-dependent cellular behaviors consistent with experiments. A machine learning analysis of the time-dependent metabolomics and metabolic fluxes highlighted the effect of introducing a complex assembly into our whole-cell model.
AB - Macromolecular complexes in the genetically minimized bacterium, JCVI-syn3A, support gene expression (RNA polymerase, ribosome, degradosome), metabolism (ABC transporters, ATP synthase), and chromosome dynamics. In this work, we further incorporate the assembly of 21 unique macromolecular complexes into the existing whole-cell kinetic model of Syn3A. The synthesis and translocation of protein subunits in membrane complexes occur through distinct pathways. A range of 2D association rates for membrane complexes were considered to guarantee a high yield of assembly, given the existing time scales of gene expression. By alleviation of the undesired kinetically trapped intermediates in ATP synthase assembly, the efficiency was improved. The assembly of RNA polymerase, ribosome, and degradosome influences the speed and efficiency of protein synthesis. Collectively, this model predicted time-dependent cellular behaviors consistent with experiments. A machine learning analysis of the time-dependent metabolomics and metabolic fluxes highlighted the effect of introducing a complex assembly into our whole-cell model.
UR - https://www.scopus.com/pages/publications/105026759630
UR - https://www.scopus.com/pages/publications/105026759630#tab=citedBy
U2 - 10.1021/acs.jpcb.5c04532
DO - 10.1021/acs.jpcb.5c04532
M3 - Article
C2 - 41427637
AN - SCOPUS:105026759630
SN - 1520-6106
VL - 130
SP - 11
EP - 32
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 1
ER -