Continual reproduction of self-assembling oligotriazole peptide nanomaterials.

Autocatalytic chemical reactions, whereby a molecule is able to catalyze its own formation from a set of precursors, mimic nature's ability to generate identical copies of relevant biomolecules, and are thought to have been crucial for the origin of life. While several molecular autocatalysts have been previously reported, coupling autocatalytic behavior to macromolecular self-assembly has been challenging. Here, we report a non-enzymatic and chemoselective methodology capable of autocatalytically producing triskelion peptides that self-associate into spherical bioinspired nanostructures. Serial transfer experiments demonstrate that oligotriazole autocatalysis successfully leads to continual self-assembly of three-dimensional nanospheres. Triskelion-based spherical architectures offer an opportunity to organize biomolecules and chemical reactions in unique, nanoscale compartments. The use of peptide-based autocatalysts that are capable of self-assembly represents a promising method for the development of self-synthesizing biomaterials, and may shed light on understanding life's chemical origins.Molecules that act as both autocatalysts and material precursors offer exciting prospects for self-synthesizing materials. Here, the authors design a triazole peptide that self-replicates and then self-assembles into nanostructures, coupling autocatalytic and assembly pathways to realize a reproducing supramolecular system

De novo vesicle formation and growth: an integrative approach to artificial cells.

The assembly of artificial cells provides a novel strategy to reconstruct life's functions and shed light on how life emerged on Earth and possibly elsewhere. A major challenge to the development of artificial cells is the establishment of simple methodologies to mimic native membrane generation. An ambitious strategy is the bottom-up approach, which aims to systematically control the assembly of highly ordered membrane architectures with defined functionality. This perspective will cover recent advances and the current state-of-the-art of minimal lipid architectures that can faithfully reconstruct the structure and function of living cells. Specifically, we will overview work related to the de novo formation and growth of biomimetic membranes. These studies give us a deeper understanding of the nature of living systems and bring new insights into the origin of cellular life

A minimal biochemical route towards de novo formation of synthetic phospholipid membranes.

All living cells consist of membrane compartments, which are mainly composed of phospholipids. Phospholipid synthesis is catalyzed by membrane-bound enzymes, which themselves require pre-existing membranes for function. Thus, the principle of membrane continuity creates a paradox when considering how the first biochemical membrane-synthesis machinery arose and has hampered efforts to develop simplified pathways for membrane generation in synthetic cells. Here, we develop a high-yielding strategy for de novo formation and growth of phospholipid membranes by repurposing a soluble enzyme FadD10 to form fatty acyl adenylates that react with amine-functionalized lysolipids to form phospholipids. Continuous supply of fresh precursors needed for lipid synthesis enables the growth of vesicles encapsulating FadD10. Using a minimal transcription/translation system, phospholipid vesicles are generated de novo in the presence of DNA encoding FadD10. Our findings suggest that alternate chemistries can produce and maintain synthetic phospholipid membranes and provides a strategy for generating membrane-based materials

In Situ Synthesis of Artificial Lipids

This review comes from a themed issue on Synthetic Biomolecules (2022); Edited by Neal K. Devaraj and Shinya TsukijiFinanciado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Lipids constitute one of the most enigmatic family of biological molecules. Although the importance of lipids as basic units of compartmental structure and energy storage is well-acknowledged, deciphering the biosynthesis and precise roles of specific lipid species has been challenging. To better understand the structure and function of these biomolecules, there is a burgeoning interest in developing strategies to produce noncanonical lipids in a controlled manner. This review covers recent advances in the area of in situ generation of synthetic lipids. Specifically, we report several approaches that constitute a powerful toolbox for achieving noncanonical lipid synthesis. We describe how these methodologies enable the direct construction of synthetic lipids, helping to address fundamental questions related to the cell biology of lipid biosynthesis, trafficking, and signaling. We envision that highlighting the current advances in artificial lipid synthesis will pave the way for broader interest into this emerging class of biomimetic molecules.Roberto J. Brea acknowledges support from Xunta de Galicia through the “Atracción de talento investigador” programme (ED431H2020/19). Roberto J. Brea also thanks the Agencia Estatal de Investigación (AEI) and the Ministerio de Ciencia e Innovación (MICINN) for his Ramón y Cajal contract (RYC2020-030065-I). The authors acknowledge funding for open access charge from Universidade da Coruña/Consorcio Interuniversitario de Galicia (CISUG)Xunta de Galicia; ED431H2020/1

Chemoselective Esterification of Natural and Prebiotic 1,2-Amino Alcohol Amphiphiles in Water

[Abstract] In cells, a vast number of membrane lipids are formed by the enzymatic O-acylation of polar head groups with acylating agents such as fatty acyl-CoAs. Although such ester-containing lipids appear to be a requirement for life on earth, it is unclear if similar types of lipids could have spontaneously formed in the absence of enzymatic machinery at the origin of life. There are few examples of enzyme-free esterification of amphiphiles in water and none that can occur in water at physiological pH using biochemically relevant acylating agents. Here we report the unexpected chemoselective O-acylation of 1,2-amino alcohol amphiphiles in water directed by Cu(II) and several other transition metal ions. In buffers containing Cu(II) ions, mixing biological 1,2-amino alcohol amphiphiles such as sphingosylphosphorylcholine with biochemically relevant acylating agents, namely, acyl adenylates and acyl-CoAs, leads to the formation of the O-acylation product with high selectivity. The resulting O-acylated sphingolipids self-assemble into vesicles with markedly different biophysical properties than those formed from their N-acyl counterparts. We also demonstrate that Cu(II) can direct the O-acylation of alternative 1,2-amino alcohols, including prebiotically relevant 1,2-amino alcohol amphiphiles, suggesting that simple mechanisms for aqueous esterification may have been prevalent on earth before the evolution of enzymes.This work was funded by the Department of Defense (W911NF-13-1-0383), the National Institutes of Health (R35GM141939), and the Agencia Estatal de Investigación (AEI) and the Ministerio de Ciencia e Innovación (MICINN) [PID2021-128113NA-I00]. Roberto J. Brea also thanks the Ministerio de Ciencia e Innovación (MICINN) and the Agencia Estatal de Investigación (AEI) for his Ramón y Cajal contract (RYC2020-030065-I). The authors thank Dr Anindya Sarkar (Boger Lab, The Scripps Research Institute) for acquiring the IR spectra and the Budin Lab (UC San Diego) for assistance with obtaining fluorescence anisotropy data.United States of America. Department of Defense; W911NF-13-1-0383United States of America. National Institutes of Health; R35GM14193

Rapid Formation of Non-canonical Phospholipid Membranes by Chemoselective Amide-Forming Ligations with Hydroxylamines

[Abstract] There has been increasing interest in methods to generate synthetic lipid membranes as key constituents of artificial cells or to develop new tools for remodeling membranes in living cells. However, the biosynthesis of phospholipids involves elaborate enzymatic pathways that are challenging to reconstitute in vitro. An alternative approach is to use chemical reactions to non-enzymatically generate natural or non-canonical phospholipids de novo. Previous reports have shown that synthetic lipid membranes can be formed in situ using various ligation chemistries, but these methods lack biocompatibility and/or suffer from slow kinetics at physiological pH. Thus, it would be valuable to develop chemoselective strategies for synthesizing phospholipids from water-soluble precursors that are compatible with synthetic or living cells Here, we demonstrate that amide-forming ligations between lipid precursors bearing hydroxylamines and α-ketoacids (KAs) or potassium acyltrifluoroborates (KATs) can be used to prepare non-canonical phospholipids at physiological pH conditions. The generated amide-linked phospholipids spontaneously self-assemble into cell-like micron-sized vesicles similar to natural phospholipid membranes. We show that lipid synthesis using KAT ligation proceeds extremely rapidly, and the high selectivity and biocompatibility of the approach facilitates the in situ synthesis of phospholipids and associated membranes in living cells.his work was supported by the National Institutes of Health (R35GM141939), the Agencia Estatal de Investigación (AEI) and the Ministerio de Ciencia e Innovación (MICINN) [PID2021-128113NA-I00]. R.J.B. also thanks the Agencia Estatal de Investigación (AEI) and the Ministerio de Ciencia e Innovación (MICINN) for his Ramón y Cajal contract (RYC2020-030065-I). I.B. acknowledges support from the National Science Foundation (MCB-2046303). The authors acknowledge the facilities, along with the scientific and technical assistance of the Dr. Mariusz Matyszewski from the cryo-EM facility and Dr. Yongxuan Su from the Molecular Mass Spectrometry Facility at UC San Diego

α,γ-Peptide nanotube templating of one-dimensional parallel fullerene arrangements

(Figure Presented) The formation and full characterization of single self-assembling α,γ-peptide nanotubes (α,γ-SPNs) is described. The introduction of C60 into cyclic peptides allows the preparation of supramolecular 1D fullerene arrangements induced by peptide nanotube formation under appropriate conditions. © 2009 American Chemical Society.This work was supported by the Spanish Ministry of Education and Science and the ERDF [SAF2007-61015 and Consolider Ingenio 2010 (CSD2007-00006)] and the Xunta de Galicia (GRC2006/ 132, PGIDIT06PXIB209018PR, PGIDIT08CSA047209PR, and R2006/ 124). The work by J.M.V. and J.L.C. was supported by Grants BFU2007- 62382/BMC from the Spanish MEC (J.M.V.) and S-0505/MAT/0283 from the Madrid Regional Government (J.M.V. and J.L.C.). C.R. and R.J.B. thank the Spanish MEC for their FPU Fellowships. We also thank Dr. Carmen Serra (Nanotechnology and Surface Analysis Service at C.A.C.T.I., University of Vigo) for her help with STM. We also thank Dowpharma for their kind gift of ENZA enzymes used in the preparation of D-Boc-γ-Acp-OH.Peer reviewe

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries