Synthetic cell division system: Controlling equal vs. unequal divisions by design

ABSTRACT 3-Methoxybenzamide (3-MBA), which is known to be an inhibitor of ADP-ribosyltransferase, inhibits cell division in Bacillus subtilis, leading to filamentation and eventually lysis of cells. Our genetic analysis of 3-MBA-resistant mutants indicated that the primary target of the drug is the cell division system involving FtsZ function during both vegetative growth and sporulation.

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Assembly of bacterial cell division protein FtsZ into dynamic biomolecular condensates

10.1101/2020.08.27.271288 ◽

2020 ◽

Author(s):

Miguel Ángel Robles-Ramos ◽

Silvia Zorrilla ◽

Carlos Alfonso ◽

William Margolin ◽

Germán Rivas ◽

...

Keyword(s):

Cell Division ◽

Bacterial Cell ◽

Bound State ◽

Bacterial Cell Division ◽

Structural Element ◽

Physiological Factors ◽

General Role ◽

E Coli ◽

Division Site ◽

Synthetic Cell

Biomolecular condensation through phase separation may be a novel mechanism to regulate bacterial processes, including cell division. Previous work revealed FtsZ, a protein essential for cytokinesis in most bacteria, and the E. coli division site selection factor SlmA form FtsZ∙SlmA biomolecular condensates. The absence of condensates composed solely of FtsZ under the conditions used in that study suggested this mechanism was restricted to nucleoid occlusion or SlmA-containing bacteria. Here we report that FtsZ alone can demix into condensates in bulk and when encapsulated in synthetic cell-like systems. Condensate assembly depends on FtsZ being in the GDP-bound state and on crowding conditions that promote its oligomerization. FtsZ condensates are dynamic and gradually convert into FtsZ filaments upon GTP addition. Notably, FtsZ lacking its C-terminal disordered region, a structural element likely to favor biomolecular condensation, also forms condensates, albeit less efficiently. The inherent tendency of FtsZ to form condensates susceptible to modulation by physiological factors, including binding partners, suggests that such mechanisms may play a more general role in bacterial cell division than initially envisioned.

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New insights into the physical processes that underpin cell division and the emergence of different cellular and multicellular structures.

10.31219/osf.io/sxc3u ◽

2019 ◽

Cited By ~ 1

Author(s):

Philip Turner ◽

Laurent Nottale ◽

John Zhao ◽

Edouard Pesquet

Keyword(s):

Cell Division ◽

Quantum Coherence ◽

Physical Processes ◽

Pauli Equation ◽

Relativistic Limit ◽

Macroscopic Quantum ◽

Synthetic Cell ◽

Quantum Phenomena ◽

A Charge ◽

The Impact

Despite decades of focused research, a detailed understanding of the fundamental physical processes that underpin biological systems (structures and processes) remains an open challenge. Within the present paper we report on biomimetic studies, which offer new insights into the process of cell division and the emergence of different cellular and multicellular structures.Experimental studies specifically investigated the impact of including different con- centrations of charged bio-molecules (cytokinin and gibberellic acid) on the growth of BaCO3 − SiO2 based structures. Results highlighted the role of charge density on the emergence of long-range order, underpinned by a negentropic process. This included the growth of synthetic cell-like structures, with the intrinsic capacity to divide and change morphology at cellular and multicellular scales.Detailed study of dividing structures supports a hypothesis that cell division is de- pendent on the establishment of a charge-induced macroscopic quantum potential and cell-scale quantum coherence, which allows a description in terms of a macroscopic Schrödinger-like equation, based on a constant different from the Planck constant. Whilst the system does not reflect full correspondence with standard quantum mechanics, many of the phenomena that we typically associate with such a system are recovered.In addition to phenomena normally associated with the Schrödinger equation, we also unexpectedly report on the emergence of intrinsic spin as a macroscopic quantum phenomena, whose origins we account for within a four-dimensional fractal space-time and a macroscopic Pauli equation, which represents the non-relativistic limit of the Dirac equation.

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The archaeal division protein CdvB1 assembles into polymers that are depolymerized by CdvC

10.1101/2021.10.07.463537 ◽

2021 ◽

Author(s):

Alberto Blanch Jover ◽

Nicola De Franceschi ◽

Daphna Fenel ◽

Winfried Weissenhorn ◽

Cees Dekker

Keyword(s):

Cell Division ◽

Lipid Membranes ◽

Membrane Binding ◽

Biochemical Assays ◽

Central Actor ◽

Main Components ◽

Insight Into ◽

Division System

AbstractThe Cdv proteins constitute the cell-division system of the Crenarchaea, in a protein machinery that is closely related to the ESCRT system of eukaryotes. The CdvB paralog CdvB1 is believed to play a major role in the constricting ring that is the central actor in cell division in the crenarchaea. Here, we present an in vitro study of purified CdvB1 from the crenarchaeon M. sedula with a combination of TEM imaging and biochemical assays. We show that CdvB1 self-assembles into filamentous polymers that are depolymerized by the action of the Vps4-homolog ATPase CdvC. Using liposome flotation assays, we show that CdvB1 binds to negatively charged lipid membranes and can be detached from the membrane by the action of CdvC. Interestingly, we find that the polymerization and the membrane binding are mutually exclusive properties of the protein. Our findings provide novel insight into one of the main components of the archaeal cell division machinery.

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Targeting Bacterial Cell Division: A Binding Site-Centered Approach to the Most Promising Inhibitors of the Essential Protein FtsZ

Antibiotics ◽

10.3390/antibiotics9020069 ◽

2020 ◽

Vol 9 (2) ◽

pp. 69 ◽

Cited By ~ 2

Author(s):

Andrea Casiraghi ◽

Lorenzo Suigo ◽

Ermanno Valoti ◽

Valentina Straniero

Keyword(s):

Cell Division ◽

Bacterial Cell ◽

Molecular Mechanisms ◽

Protein A ◽

Bactericidal Effect ◽

Bacterial Cell Division ◽

Z Ring ◽

Main Protein ◽

Ftsz Inhibitors ◽

Division System

Binary fission is the most common mode of bacterial cell division and is mediated by a multiprotein complex denominated the divisome. The constriction of the Z-ring splits the mother bacterial cell into two daughter cells of the same size. The Z-ring is formed by the polymerization of FtsZ, a bacterial protein homologue of eukaryotic tubulin, and it represents the first step of bacterial cytokinesis. The high grade of conservation of FtsZ in most prokaryotic organisms and its relevance in orchestrating the whole division system make this protein a fascinating target in antibiotic research. Indeed, FtsZ inhibition results in the complete blockage of the division system and, consequently, in a bacteriostatic or a bactericidal effect. Since many papers and reviews already discussed the physiology of FtsZ and its auxiliary proteins, as well as the molecular mechanisms in which they are involved, here, we focus on the discussion of the most compelling FtsZ inhibitors, classified by their main protein binding sites and following a medicinal chemistry approach.

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Construction of intracellular asymmetry and asymmetric division in Escherichia coli

Nature Communications ◽

10.1038/s41467-021-21135-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Da-Wei Lin ◽

Yang Liu ◽

Yue-Qi Lee ◽

Po-Jiun Yang ◽

Chia-Tse Ho ◽

...

Keyword(s):

Escherichia Coli ◽

Cell Division ◽

Cell Biology ◽

Design Principle ◽

Asymmetric Cell Division ◽

Caulobacter Crescentus ◽

Asymmetric Division ◽

Spatial Gradient ◽

Natural Systems ◽

Synthetic Cell

AbstractThe design principle of establishing an intracellular protein gradient for asymmetric cell division is a long-standing fundamental question. While the major molecular players and their interactions have been elucidated via genetic approaches, the diversity and redundancy of natural systems complicate the extraction of critical underlying features. Here, we take a synthetic cell biology approach to construct intracellular asymmetry and asymmetric division in Escherichia coli, in which division is normally symmetric. We demonstrate that the oligomeric PopZ from Caulobacter crescentus can serve as a robust polarized scaffold to functionalize RNA polymerase. Furthermore, by using another oligomeric pole-targeting DivIVA from Bacillus subtilis, the newly synthesized protein can be constrained to further establish intracellular asymmetry, leading to asymmetric division and differentiation. Our findings suggest that the coupled oligomerization and restriction in diffusion may be a strategy for generating a spatial gradient for asymmetric cell division.

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