Establishing Communication Between Artificial Cells

Communication between artificial cells is essential for the realization of complex dynamical behaviors at the multi-cell level. It is also an important prerequisite for modular systems design, because it determines how spatially separated functional modules can coordinate their actions. Among others, molecular communication is required for artificial cell signaling, synchronization of cellular behaviors, computation, group-level decision-making processes and pattern formation in artificial tissues. In this review, an overview of various recent approaches to create communicating artificial cellular systems is provided. In this context, important physicochemical boundary conditions that have to be considered for the design of the communicating cells are also described, and a survey of the most striking emergent behaviors that may be achieved in such systems is given.     

Enhancing the Catalytic Activity of MOF-808 Towards Peptide Bond Hydrolysis through Synthetic Modulations

The performance of MOFs in catalysis is largely derived from structural features, and much work has focused on introducing structural changes such as defects or ligand functionalisation to boost the reactivity of the MOF. However, the effects of different parameters chosen for the synthesis on the catalytic reactivity of the resulting MOF remains poorly understood. Here, we evaluate the role of metal precursor on the reactivity of Zr-based MOF-808 towards hydrolysis of the peptide bond in the glycylglycine model substrate. In addition, the effect of synthesis temperature and duration has been investigated. Surprisingly, the metal precursor was found to have a large influence on the reactivity of the MOF, surpassing the effect of particle size or number of defects. Additionally, we show that by careful selection of the Zr-salt precursor and temperature used in MOF syntheses, equally active MOF catalysts could be obtained after a 20 minute synthesis compared to 24 h synthesis.     

MaxSynBio: Avenues Towards Creating Cells from the Bottom Up

A large German research consortium mainly within the Max Planck Society (“MaxSynBio”) was formed to investigate living systems from a fundamental perspective. The research program of MaxSynBio relies solely on the bottom‐up approach to synthetic biology. MaxSynBio focuses on the detailed analysis and understanding of essential processes of life through modular reconstitution in minimal synthetic systems. The ultimate goal is to construct a basic living unit entirely from non‐living components. The fundamental insights gained from the activities in MaxSynBio could eventually be utilized for establishing a new generation of biotechnological processes, which would be based on synthetic cell constructs that replace the natural cells currently used in conventional biotechnology.     

Towards Self‐Assembled Hybrid Artificial Cells: Novel Bottom‐Up Approaches to Functional Synthetic Membranes

There has been increasing interest in utilizing bottom‐up approaches to develop synthetic cells. A popular methodology is the integration of functionalized synthetic membranes with biological systems, producing “hybrid” artificial cells. This Concept article covers recent advances and the current state‐of‐the‐art of such hybrid systems. Specifically, we describe minimal supramolecular constructs that faithfully mimic the structure and/or function of living cells, often by controlling the assembly of highly ordered membrane architectures with defined functionality. These studies give us a deeper understanding of the nature of living systems, bring new insights into the origin of cellular life, and provide novel synthetic chassis for advancing synthetic biology.     

第一个人工合成元素锝：化学家与物理学家合作的结晶

1871年，门捷列夫依据元素周期律和元素周期表预见了“类锰”（即锝元素）的存在；至20世纪，随着科学家对原子核变化的研究进展、回旋加速器的发明以及人工放射性元素的发现，化学家和物理学家一起用回旋加速器加速的氚核轰击钼靶得到了锝元素。锝成为了第一个人工合成的元素，是化学家与物理学家合作的结晶。它的发现不仅显示了先进的科学方法和科学仪器的重要作用，也证明了学科间合作的重要性。     

Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors

Receptor tyrosine kinases (RTKs) are key regulators of cellular functions in metazoans. In vertebrates, RTKs are mostly activated by polypeptides but are not naturally sensitive to amino acids or light. Taking inspiration from Venus kinase receptors (VKRs), an atypical family of RTKs found in nature, we have transformed the human insulin (hIR) and hepatocyte growth factor receptor (hMET) into glutamate receptors by replacing their extracellular binding domains with the ligand‐binding domain of metabotropic glutamate receptor type 2 (mGluR2). We then imparted light sensitivity through covalent attachment of a synthetic glutamate‐based photoswitch via a self‐labelling SNAP tag. By employing a Xenopus laevis oocyte kinase activity assay, we demonstrate how these chimeric RTKs, termed light‐controlled human insulin receptor (LihIR) and light‐controlled human MET receptor (LihMET), can be used to exert optical control over the insulin or MET signaling pathways. Our results outline a potentially general strategy to convert RTKs into photoreceptors.     

Two‐Dimensional Polymers: Just a Dream of Synthetic Chemists?

In light of the considerable impact synthetic 2D polymers are expected to have on many fundamental and applied aspects of the natural and engineering sciences, it is surprising that little research has been carried out on these intriguing macromolecules. Although numerous approaches have been reported over the last several decades, the synthesis of a one monomer unit thick, covalently bonded molecular sheet with a long‐range ordered (periodic) internal structure has yet to be achieved. This Review provides an overview of these approaches and an analysis of how to synthesize 2D polymers. This analysis compares polymerizations in (initially) a homogeneous phase with those at interfaces and considers structural aspects of monomers as well as possibly preferred connection modes. It also addresses issues such as shrinkage as well as domain and crack formation, and briefly touches upon how the chances for a successful structural analysis of the final product can possibly be increased.     

A Molecular Tête-à-Tête Arranged by a Designed Adaptor Protein

Come together: The joining of two miniature proteins binding different protein targets in a synthetic adaptor protein is a novel way to induce proximity between proteins. The formation of a ternary complex was shown to cause the phosphorylation of a noninherent substrate (hDM2) by the kinase Hck. The approach holds promise to become a genetically encodable system to redirect enzyme activities in vivo.     

Parallel Optimization of Synthetic Pathways within the Network of Organic Chemistry

Finding a needle in a haystack: The number of possible synthetic pathways leading to the desired target of a synthesis can be astronomical (10(19) within five synthetic steps). Algorithms are described that navigate through the entire known chemical-synthetic knowledge to identify optimal synthetic pathways. Examples are provided to illustrate single-target optimization and parallel optimization of syntheses leading to multiple targets.     

Capillary electrophoresis of signaling molecules

The emerging field of quantitative systems biology uses high-throughput bioanalytical measurements to gain a deeper understanding of biological phenomena. With the advent of instrumentation platforms, capillary electrophoresis spans a very wide range of biological applications. This short article focuses on the exploitation of capillary electrophoresis for the systems-level analysis of cell signaling molecules.     

Yeast Synthetic Biology for the Production of Lycium barbarum Polysaccharides

The fruit of Lycium barbarum L. (goji berry) is used as traditional Chinese medicine, and has the functions of immune regulation, anti-tumor, neuroprotection, anti-diabetes, and anti-fatigue. One of the main bioactive components is L. barbarum polysaccharide (LBP). Nowadays, LBP is widely used in the health market, and it is extracted from the fruit of L. barbarum. The planting of L. barbarum needs large amounts of fields, and it takes one year to harvest the goji berry. The efficiency of natural LBP production is low, and the LBP quality is not the same at different places. Goji berry-derived LBP cannot satisfy the growing market demands. Engineered Saccharomyces cerevisiae has been used for the biosynthesis of some plant natural products. Recovery of LBP biosynthetic pathway in L. barbarum and expression of them in engineered S. cerevisiae might lead to the yeast LBP production. However, information on LBP biosynthetic pathways and the related key enzymes of L. barbarum is still limited. In this review, we summarized current studies about LBP biosynthetic pathway and proposed the strategies to recover key enzymes for LBP biosynthesis. Moreover, the potential application of synthetic biology strategies to produce LBP using engineered S. cerevisiae was discussed.     

Breaking the Bottleneck in Anticancer Drug Development: Efficient Utilization of Synthetic Biology

Natural products have multifarious bioactivities against bacteria, fungi, viruses, cancers and other diseases due to their diverse structures. Nearly 65% of anticancer drugs are natural products or their derivatives. Thus, natural products play significant roles in clinical cancer therapy. With the development of biosynthetic technologies, an increasing number of natural products have been discovered and developed as candidates for clinical cancer therapy. Here, we aim to summarize the anticancer natural products approved from 1950 to 2021 and discuss their molecular mechanisms. We also describe the available synthetic biology tools and highlight their applications in the development of natural products.     

Synthetic multivalent ligands as probes of signal transduction

Cell-surface receptors acquire information from the extracellular environment and coordinate intracellular responses. Many receptors do not operate as individual entities, but rather as part of dimeric or oligomeric complexes. Coupling the functions of multiple receptors may endow signaling pathways with the sensitivity and malleability required to govern cellular responses. Moreover, multireceptor signaling complexes may provide a means of spatially segregating otherwise degenerate signaling cascades. Understanding the mechanisms, extent, and consequences of receptor co-localization and interreceptor communication is critical; chemical synthesis can provide compounds to address the role of receptor assembly in signal transduction. Multivalent ligands can be generated that possess a variety of sizes, shapes, valencies, orientations, and densities of binding elements. This Review focuses on the use of synthetic multivalent ligands to characterize receptor function.     

甘脲类分子胶囊受体合成方法的研究进展

甘脲类分子胶囊是一类独特的由非共价键弱相互作用力组装而成的人工受体, 在分子识别、自组装、分子微反应器、智能材料等方面得到了广泛而深入的研究. 系统综述了网球型(Tennis ball)、垒球型(Softball)、足球型(Football)及圆盘型(Jelly Doughnut)等分子胶囊的合成方法.     

Post‐Synthetic Modification of Zr‐Metal–Organic Frameworks through Cycloaddition Reactions

Cycloaddition reactions are highly attractive for post‐synthetic modification of metal–organic frameworks (MOFs). We report herein on cycloaddition reactions with PIZOF(R¹,R²)s, which are porous interpenetrated Zr‐based MOFs with Zr₆O₄(OH)₄(CO₂)₁₂ as the nodes and the dicarboxylates ^?O₂C[PE‐P(R¹,R²)‐EP]CO₂^? (P: phenylene, E: ethynylene; R¹, R²: side chains at the central phenylene unit) as the linkers. 1,3‐Dipolar cycloaddition between the pendant ethyne moieties of PIZOF(OMe,OCH₂C?CH) and 4‐methylbenzyl azide resulted in 98 % conversion of the ethyne groups. Reactions of PIZOF(OMe,O(CH₂)₃furan) with maleimide, N‐methylmaleimide, and N‐phenylmaleimide converted 98, 99, and 89 % of the furan moieties into the Diels–Alder adducts. However, no reaction occurred with maleic anhydride. High‐resolution ¹H NMR spectra were crucial in determining the conversion and identifying the reaction products. Of all the reagents (NaOD/D₂O, D₂SO₄, Bu₄NF, CsF, CsF/DCl, and KHF₂) tested for the disassembly of the PIZOFs in [D₆]DMSO, the combination of CsF and DCl was found to be the best. The disassembly at room temperature was fast (5–15 min), and after the addition of K₂CO₃ the ¹H NMR data were identical to those of the diacids (=protonated linkers) dissolved in pure DMSO. This allowed for simple structure elucidation through data comparison. CsF/DCl dissolves not only PIZOFs but also the hydrolytically very stable UiO‐66.     

Factors Determining the Selection of Organic Reactions by Medicinal Chemists and the Use of These Reactions in Arrays (Small Focused Libraries)

Synthetic organic reactions are a fundamental enabler of small‐molecule drug discovery, and the vast majority of medicinal chemists are initially trained—either at universities or within industry—as synthetic organic chemists. The sheer breadth of synthetic methodology available to the medicinal chemist represents an almost endless source of innovation. But what reactions do medicinal chemists use in drug discovery? And what criteria do they use in selecting synthetic methodology? Why are arrays (small focused libraries) so powerful in the lead‐optimization process? In this Minireview, we suggest some answers to these questions and also describe how we have tried to expand the number of robust reactions available to the medicinal chemist.     

Towards a Synthetic Biology Toolset for Metallocluster Enzymes in Biosynthetic Pathways: What We Know and What We Need

Microbes are routinely engineered to synthesize high-value chemicals from renewable materials through synthetic biology and metabolic engineering. Microbial biosynthesis often relies on expression of heterologous biosynthetic pathways, i.e., enzymes transplanted from foreign organisms. Metallocluster enzymes are one of the most ubiquitous family of enzymes involved in natural product biosynthesis and are of great biotechnological importance. However, the functional expression of recombinant metallocluster enzymes in live cells is often challenging and represents a major bottleneck. The activity of metallocluster enzymes requires essential supporting pathways, involved in protein maturation, electron supply, and/or enzyme stability. Proper function of these supporting pathways involves specific protein–protein interactions that remain poorly characterized and are often overlooked by traditional synthetic biology approaches. Consequently, engineering approaches that focus on enzymatic expression and carbon flux alone often overlook the particular needs of metallocluster enzymes. This review highlights the biotechnological relevance of metallocluster enzymes and discusses novel synthetic biology strategies to advance their industrial application, with a particular focus on iron-sulfur cluster enzymes. Strategies to enable functional heterologous expression and enhance recombinant metallocluster enzyme activity in industrial hosts include: (1) optimizing specific maturation pathways; (2) improving catalytic stability; and (3) enhancing electron transfer. In addition, we suggest future directions for developing microbial cell factories that rely on metallocluster enzyme catalysis.