Predicting EC numbers for chemical reactions enables efficient enzymatic annotations for computer-aided synthesis planning. However, conventional machine learning approaches encounter challenges due to data scarcity and class imbalance. Here, we introduce CLAIRE (Contrastive Learning-based AnnotatIon for Reaction's EC), a novel framework leveraging contrastive learning, pre-trained language model-based reaction embeddings, and data augmentation to address these limitations.
View Article and Find Full Text PDFThe concept of genetic code expansion (GCE) has revolutionized the field of chemical and synthetic biology, enabling the site-specific incorporation of noncanonical amino acids (ncAAs) into proteins, thus opening new avenues in research and applications across biology and medicine. In this review, we cover the principles of GCE, including the optimization of the aminoacyl-tRNA synthetase (aaRS)/tRNA system and the advancements in translation system engineering. Notable developments include the refinement of aaRS/tRNA pairs, enhancements in screening methods, and the biosynthesis of noncanonical amino acids.
View Article and Find Full Text PDFPigments, as coloured secondary metabolites, endow the world with a rich palette of colours. They primarily originate from plants and microorganisms and play crucial roles in their survival and adaptation processes. In this article, we categorize pigments based on their chemical structure into flavonoids, carotenoids, pyrroles, quinones, azaphilones, melanins, betalains, flavins, and others.
View Article and Find Full Text PDFPromoter-centric genetic tools play a crucial role in controlling gene expression for various applications, such as strain engineering and synthetic biology studies. Hence, a critical need persists for the development of robust gene expression tools. are well-known prolific producers of natural products and exceptional surrogate hosts for the production of high-value chemical compounds and enzymes.
View Article and Find Full Text PDFInt J Biol Macromol
June 2024
Thermophilic proteins are important for academic research and industrial processes, and various computational methods have been developed to identify and screen them. However, their performance has been limited due to the lack of high-quality labeled data and efficient models for representing protein. Here, we proposed a novel sequence-based thermophilic proteins prediction framework, called ThermoFinder.
View Article and Find Full Text PDFStreptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we proposed that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis.
View Article and Find Full Text PDFFunctionalizing materials with biomacromolecules such as enzymes has broad applications in biotechnology and biomedicine. Here, we introduce a grafting method mediated by living cells to functionalize materials. We use polymeric scaffolds to trap engineered bacteria and micron-sized particles with chemical groups serving as active sites for grafting.
View Article and Find Full Text PDFThe evolution of pathway enzymes enhances the biosynthesis of high-value chemicals, crucial for pharmaceutical, and agrochemical applications. However, unpredictable evolutionary landscapes of pathway genes often hinder successful evolution. Here, the presence of complex epistasis is identifued within the representative naringenin biosynthetic pathway enzymes, hampering straightforward directed evolution.
View Article and Find Full Text PDFPlitidepsin (or dehydrodidemnin B), an approved anticancer drug, belongs to the didemnin family of cyclic depsipeptides, which are found in limited quantities in marine tunicate extracts. Herein, we introduce a new approach that integrates microbial and chemical synthesis to generate plitidepsin and its analogues. We screened a Tistrella strain library to identify a potent didemnin B producer, and then introduced a second copy of the didemnin biosynthetic gene cluster into its genome, resulting in a didemnin B titer of approximately 75 mg/L.
View Article and Find Full Text PDFPrediction of enzyme kinetic parameters is essential for designing and optimizing enzymes for various biotechnological and industrial applications, but the limited performance of current prediction tools on diverse tasks hinders their practical applications. Here, we introduce UniKP, a unified framework based on pretrained language models for the prediction of enzyme kinetic parameters, including enzyme turnover number (k), Michaelis constant (K), and catalytic efficiency (k / K), from protein sequences and substrate structures. A two-layer framework derived from UniKP (EF-UniKP) has also been proposed to allow robust k prediction in considering environmental factors, including pH and temperature.
View Article and Find Full Text PDFTyrian purple (6,6'-Dibromoindigo) is an ancient precious dye, which possesses remarkable properties as a biocompatible semiconductor material. Recently, biosynthesis has emerged as an alternative for the sustainable production of Tyrian purple from a natural substrate. However, the selectivity issue in enzymatic tryptophan (Trp) and bromotryptophan (6-Br-Trp) degradation was an obstacle for obtaining high-purity Tyrian purple in a single cell biosynthesis.
View Article and Find Full Text PDFChromoplasts act as a metabolic sink for carotenoids, in which plastoglobules serve as versatile lipoprotein particles. PGs in chloroplasts have been characterized. However, the features of PGs from non-photosynthetic plastids are poorly understood.
View Article and Find Full Text PDFCannabinoids are important therapeutical molecules for human ailments, cancer treatment, and SARS-CoV-2. The central cannabinoid, cannabigerolic acid (CBGA), is generated from geranyl pyrophosphate and olivetolic acid by Cannabis sativa prenyltransferase (CsPT4). Despite efforts to engineer microorganisms such as Saccharomyces cerevisiae (S.
View Article and Find Full Text PDFThe gut microbiota plays a significant role in influencing human immunity, metabolism, development, and behavior by producing a wide range of metabolites. While there is accumulating data on several microbiota-derived small molecules that contribute to host health and disease, our knowledge regarding the molecular mechanisms underlying metabolite-mediated microbe-host interactions remains limited. This is primarily due to the lack of efficient genetic tools for most commensal bacteria, especially those belonging to the dominant phyla Bacteroides spp.
View Article and Find Full Text PDFIntroduction: Disorders of consciousness (DOC) result from neural system injury and manifest as changes in arousal or awareness. This systematic review and meta-analysis aimed to investigate the therapeutic effects of non-invasive brain stimulation (NIBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), on consciousness dysfunction in patients with brain disorders.
Methods: Literature was systematically searched in Medline, Embase, Cochrane database, Web of Science, EBSCO from inception to May 2023.
Activating inert substrates is a challenge in nature and synthetic chemistry, but essential for creating functionally active molecules. In this work, we used a combinatorial optimization approach to assemble cytochrome P450 monooxygenases (CYPs) and reductases (CPRs) to achieve a target product profile. By creating 110 CYP-CPR pairs and iteratively screening different pairing libraries, we demonstrated a framework for establishing a CYP network that catalyzes six oxidation reactions at three different positions of a chemical scaffold.
View Article and Find Full Text PDFCyanobacterial harmful algal blooms (CyanoHABs) pose significant threats to human health and natural ecosystems worldwide, primarily caused by water eutrophication, increased surface water temperature, and co-occurring microorganisms. Urgent action is needed to develop an eco-friendly solution to effectively curb the proliferation of CyanoHABs. Sophorolipids (SLs) are fully biodegradable biosurfactants synthesized by .
View Article and Find Full Text PDFGlucosinolates (GSLs) and their degradation products in radish confer plant defense, promote human health, and generate pungent flavor. However, the intact GSLs in radish have not been investigated comprehensively yet. Here, an accurate qualitative and quantitative analyses of 15 intact GSLs from radish, including four major GSLs of glucoraphasatin (GRH), glucoerucin (GER), glucoraphenin (GRE), and 4-methoxyglucobrassicin (4MGBS), were conducted using UHPLC-HRMS/MS in combination with UHPLC-QqQ-MS/MS.
View Article and Find Full Text PDFGalactose-inducible () promoters have been widely used in metabolic engineering in for production of valuable products. Endogenous promoters and transcription factors have often been engineered to improve promoter activities. Heterologous promoters and activator (Gal4p-like transcriptional activators), although existing in other yeasts or fungi, have not been well explored.
View Article and Find Full Text PDFThe advances in determining the total structure of atomically precise metal nanoclusters have prompted extensive exploration into the origins of chirality in nanoscale systems. While chirality is generally transferrable from the surface layer to the metal-ligand interface and kernel, we present here an alternative type of gold nanoclusters (138 gold core atoms with 48 2,4-dimethylbenzenethiolate surface ligands) whose inner structures are not asymmetrically induced by chiral patterns of the outermost aromatic substituents. This phenomenon can be explained by the highly dynamic behaviors of aromatic rings in the thiolates assembled via π - π stacking and C - H···π interactions.
View Article and Find Full Text PDFSaccharomyces cerevisiae is a robust cell factory to secrete or surface-display cellulase and amylase for the conversion of agricultural residues into valuable chemicals. Engineering the secretory pathway is a well-known strategy for overproducing these enzymes. Although cell wall biosynthesis can be tightly linked to the secretory pathway by regulation of all involved processes, the effect of its modifications on protein production has not been extensively studied.
View Article and Find Full Text PDFValerolactam is a monomer used to manufacture high-value nylon-5 and nylon-6,5. However, the biological production of valerolactam has been limited by the inadequate efficiency of enzymes to cyclize 5-aminovaleric acid to produce valerolactam. In this study, we engineered Corynebacterium glutamicum with a valerolactam biosynthetic pathway consisting of DavAB from Pseudomonas putida to convert L-lysine to 5-aminovaleric acid and β-alanine CoA transferase (Act) from Clostridium propionicum to produce valerolactam from 5-aminovaleric acid.
View Article and Find Full Text PDFBackground: Since the discovery of rehabilitation as an intervention for rotator cuff injury, its impact on the recovery of rotator cuff injury has attracted crucial attention, and the number of related studies is increasing worldwide. There were no bibliometric and visualized analysis studies in this field. This study aimed to investigate the research hotpots and trends in the rehabilitation of rotator cuff injury bibliometric and visualized analysis and to identify the future development of clinical practice.
View Article and Find Full Text PDFTyrian purple, mainly composed of 6, 6'-dibromoindigo, is a precious dye extracted from sea snails. In this study, we found Tyrian purple can be selectively produced by a bacterial strain GS-2 when fed with 6-bromotryptophan in the presence of tryptophan. This GS-2 strain was then identified as based on bacterial genome sequencing analysis.
View Article and Find Full Text PDF