Synthetic biology

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Optogenetic, known as the method of 21 centuries, combines optic and genetic engineering to precisely control photosensitive proteins for manipulation of a broad range of cellular functions, such as flux of ions, protein oligomerization and dissociation, cellular intercommunication, and so on. In this technique, light is conventionally delivered to targeted cells through optical fibers or micro light-emitting diodes, always suffering from high invasiveness, wide-field illumination facula, strong absorption, and scattering by nontargeted endogenous substance...

Cadaverine is a critical C5 monomer for the production of polyamides. Pyridoxal 5'-phosphate (PLP), as a crucial cofactor for the key enzyme lysine decarboxylase in the cadaverine biosynthesis pathway, has seen a persistent shortage, leading to limitations in cadaverine production. To address this issue, a dual-pathway strategy was implemented, synergistically enhancing both endogenous and heterologous PLP synthesis modules and resulting in improved PLP synthesis. Subsequently, a growth-stage-dependent molecular switch was introduced to balance the precursor competition between PLP synthesis and cell growth...

Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long-term therapy. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula, Senna alexandrina, and Cassia occidentalis from family Fabaceae and understand their interaction mechanism with hypertension targeted genes, using network pharmacology and molecular docking...

A group of bacterial proteases, the Pro-Pro endopeptidases (PPEPs), possess the unique ability to hydrolyze proline-proline bonds in proteins. Since a protease's function is largely determined by its substrate specificity, methods that can extensively characterize substrate specificity are valuable tools for protease research. Previously, we achieved an in-depth characterization of PPEP prime-side specificity. However, PPEP specificity is also determined by the non-prime-side residues in the substrate. To gain a more complete insight into the determinants of PPEP specificity, we characterized the non-prime- and prime-side specificity of various PPEPs using a combination of synthetic combinatorial peptide libraries and mass spectrometry...

The design of artificial, synthetic cells is a fundamentally important and fast-developing field of science. Of the diverse attributes of cellular life, artificial transmembrane signaling across the biomolecular barriers remains a high challenge with only a few documented successes. Herein, the study achieves signaling across lipid bilayers and connects an exofacial enzymatic receptor activation to an intracellular biochemical catalytic response using an artificial receptor. The mechanism of signal transduction for the artificial receptor relies on the triggered decomposition of a self-immolative linker...

Molecular hybridization is a rational design strategy used to create new ligands or pro-totypes by identifying and combining specific pharmacophoric subunits from the molecular struc-tures of two or more known bioactive derivatives. Molecular hybridization is a valuable technique in drug discovery, enabling the modulation of unwanted side effects and the creation of potential dual-acting drugs that combine the effects of multiple therapeutic agents. Indole-triazole conju-gates have emerged as promising candidates for new drug development...

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease that affects both the articular and extra-articular structures, leading to significant joint damage, disability and excess mortality. The treatment algorithm of RA has changed tremendously in the past 1-2 decades because of the emergence of novel biological therapies that target different mechanisms of action in addition to TNFα. AREAS COVERED: This article summarizes the evidence and safety of the non-TNF biological DMARDs in the treatment of RA, including those that target B cells, T-cell co-stimulation, interleukin (IL)-6 and granulocyte-monocyte colony-stimulating factor (GM-CSF)...

Geminal, multi-halogenated functional groups are widespread in natural products and pharmaceuticals, yet no synthetic methodologies exist that enable selective multi-halogenation of unactivated C-H bonds. Biocatalysts are powerful tools for late-stage C-H functionalization, as they operate with high degrees of regio-, chemo-, and stereoselectivity. 2-oxoglutarate (2OG)-dependent non-heme iron halogenases chlorinate and brominate aliphatic C-H bonds offering a solution for achieving these challenging transformations...

Ion channels are biological transistors that control ionic flux across cell membranes to regulate electrical transmission and signal transduction. They are found in all biological membranes and their conductive states are frequently disrupted in human diseases. Organelle ion channels are among the most resistant to functional and pharmacological interrogation. Traditional channel protein reconstitution methods rely upon exogenous expression and/or purification from endogenous cellular sources which are frequently contaminated by resident ionophores...

Plastic waste discarded into aquatic environments gradually degrades into smaller fragments, known as microplastics (MPs), which range in size from 0.05 to 5 mm. The ubiquity of MPs poses a significant threat to aquatic ecosystems and, by extension, human health, as these particles are ingested by various marine organisms including zooplankton, crustaceans, and fish, eventually entering the human food chain. This contamination threatens the entire ecological balance, encompassing food safety and the health of aquatic systems...

Microbial communities are shaped by the complex interactions among organisms and the environment. Genome-scale metabolic models (GEMs) can provide deeper insights into the complexity and ecological properties of various microbial communities, revealing their intricate interactions. Many researchers have modified GEMs for the microbial communities based on specific needs. Thus, GEMs need to be comprehensively summarized to better understand the trends in their development. In this review, we summarized the key developments in deciphering and designing microbial communities using different GEMs...

CRISPR-Cas9 and novel cas fusion proteins leveraging specific DNA targeting ability combined with deaminases or reverse transcriptases have revolutionized genome editing. However, their efficacy heavily relies upon protein variants, targeting single guide RNAs, and surrounding DNA sequence context within the targeted loci. This necessitates the need for efficient and rapid screening methods to evaluate these editing reagents and designs. Existing plasmid-based reporters lack flexibility, being fixed to specific DNA sequences, hindering direct comparisons between various editing approaches...

Benzofurans have intrigued both pharmaceutical researchers and chemists owing to the medicinal usage of their derivatives against copious disease-causing agents (i.e., bacteria, viruses, and tumors). These heterocyclic scaffolds are pervasively encountered in a number of natural products and drugs. The ever-increasing utilization of benzofuran derivatives as pharmaceutical agents persuaded the chemists to devise novel and facile methodological approaches to assemble the biologically potent benzofuran nucleus...

The emergence of coronavirus disease 2019 (COVID-19), a novel identified pneumonia resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has significantly impacted and posed significant challenges to human society. The papain-like protease (PLpro) found in the nonstructural protein 3 of SARS-CoV-2 plays a vital role in viral replication. Moreover, PLpro disrupts the host immune response by cleaving ubiquitin and interferon-stimulated gene 15 from host proteins. Consequently, PLpro has emerged as a promising drug target against SARS-CoV-2 infection...

Amadori compounds (ACs) are key Maillard intermediates in various foods after thermal processing, and are also important non-saponin components in red ginseng. Currently, due to the difficulty in obtaining AC standards, the determination of multiple ACs is limited and far from optimal. In this study, an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated. A green synthetic method was developed for arginyl-fructosyl-glucose (AFG), the major AC in red ginseng with potential health benefits...

BACKGROUND: Pyridine and its derivatives play a vital role in medicinal chemistry, serving as key scaffolds for drugs. The ability to bind to biological targets makes pyridine compounds significant, sparking interest in creating new pyridine-based drugs. Thus, the purpose of the research is to synthesize new thioalkyl derivatives of pyridine, predict their biological spectrum, study their psychotropic properties, and based on these findings, perform structure-activity relationships to assess pharmacophore functional groups...

With the gradual increase in environmental awareness and the growing demand for food safety, sustainable and environmentally friendly cellulose-based materials have become a promising alternative to petroleum-based plastics. However, in practice, packaging materials prepared from cellulose-based materials still have some unsatisfactory properties, such as monofunctionality, low transparency, and lack of UV shielding, antibacterial or antioxidant properties. Herein, a novel synthetic strategy is proposed in this paper, specifically, tannic acid (TA), a green natural extract with antibacterial and antioxidant properties, is used as a plasticizer and cross-linker, and oxidized cellulose nanocellulose (TOCN) modified with folic acid (FA) grafting is blended with TA, and cellulose-based biomass thin films with ultraviolet (UV) shielding, antibacterial, and antioxidant properties have been successfully prepared by using a simple vacuum-assisted filtration...

At the best conditions of the bioprocess (30 °C, pH 7.0, 3.0 g/L NaCl) were obtained 0.66 g/L cell concentration, 3.3 g/L of bioemulsifier, which showed high emulsifying activity (53 % ± 2), reducing the surface tension of the water in 47.2 % (38 mN/m). The polymeric structure of the purified bioemulsifier comprised a carbohydrate backbone composed of hexose-based amino sugars with a monomeric mass of 1099 Da, structurally similar to emulsan. A. venetianus bioemulsifier is non-phytotoxic (GI% > 80 %) against Ocimum basilicum and Brassica oleracea and non-cytotoxic (LC50 5794 mg/L) against Artemia salina, being safe local organisms in comparison to other less eco-friendly synthetic emulsifiers...

Actinomycetes, a diverse group of bacteria with filamentous growth characteristics, have long captivated researchers and biochemists for their prolific production of secondary metabolites. Among the myriad roles played by actinomycete secondary metabolites, their historical significance in the field of biocontrol stands out prominently. The fascinating journey begins with the discovery of antibiotics, where renowned compounds like streptomycin, tetracycline, and erythromycin revolutionized medicine and agriculture...