Neurodegenerative diseases are the leading cause of human disability and immensely reduce patients’ life span and quality. The diseases are characterized by the functional loss of neuronal cells and share several common pathogenic mechanisms involving the malfunction, structural distortion, or aggregation of multiple key regulatory proteins. Cellular phase separation is the formation of biomolecular condensates that regulate numerous biological processes, including neuronal development and synaptic signaling transduction. Aberrant phase separation may cause protein aggregation that is a general phenomenon in the neuronal cells of patients suffering neurodegenerative diseases. In this review, we summarize the pathological causes of common neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, among others. We discuss the regulation of key amyloidogenic proteins with an emphasis of their aberrant phase separation and aggregation. We also introduce the approaches as potential therapeutic strategies to ameliorate neurodegenerative diseases through intervening protein aggregation. Overall, this review consolidates the research findings of phase separation and aggregation caused by misfolded proteins in a context of neurodegenerative diseases.

Methylxanthines are ubiquitous purine alkaloids in nature and have rich biological activities and functions. Today, the demand for methylxanthine is increasing but its production is low. This issue prevents its widespread use in many industrial fields, such as pharmaceuticals, food manufacturing, and chemical engineering. To address these issues, this review provides a comprehensive and systematic exploration of methylxanthines, delving into their biological structures, detailed biosynthetic pathways, and the latest research trends. These findings serve as valuable references for researchers, fostering advancements in the optimization of synthesis processes for methylxanthines and their derivatives and promoting their application across diverse industrial fields, such as medicine, food, and chemical engineering. By bridging fundamental research and practical applications, this work aims to advance the understanding of methylxanthine compounds, enhance their production efficiency, and contribute to healthcare and technological progress.

Mandelic acid (MA) is a valuable α-hydroxy acid with applications in pharmaceuticals, cosmetics, and fine chemicals. While chemical synthesis is well established, concerns over toxicity and sustainability have driven interest in microbial production. Here, we engineered Escherichia coli for de novo MA biosynthesis by integrating enzyme screening, metabolic flux optimization, and pathway regulation. We first screened and identified an efficient hydroxymandelate synthase (HMAS) homolog from Actinosynnema mirum for MA synthesis, and subsequently enhanced the shikimate pathway along with the supply of the precursors erythrose-4-phosphate (E4P) and phosphoenolpyruvate (PEP). Additionally, CRISPR interference (CRISPRi) was employed to repress competing pathways and redirect flux toward MA production. High-cell-density cultivation (HCDC) in a 5 L bioreactor demonstrated the strain’s industrial potential, achieving an MA titer of 9.58 g/L, the highest reported for microbial production. This study provides a systematic metabolic engineering approach for efficient MA biosynthesis from glucose, offering a foundation for sustainable large-scale production, demonstrating not only genetic-level optimizations, but also effective process scaling through high-cell-density cultivation, highlighting the power of pathway engineering in microbial cell factories.

Silk and silk-like proteins emerge as programmable building blocks for high-performance fiber materials because they can integrate mechanical robustness, biological compatibility, environmental responsiveness, and degradability within genetically defined polymers. Synthetic biology now enables precise control over protein sequence, repeat number, molecular weight, and modular architecture, creating opportunities to design fibers beyond naturally harvested silks. However, application-ready protein fibers require coordinated control across multiple length scales, from sequence-encoded motifs and molecular assembly to spinning-induced alignment, hierarchical network formation, and final property profiles. This review discusses recent advances in engineering silk and silk-like proteins into mechanically and functionally optimized fibers. We highlight how crystallite-forming motifs, amorphous domains, terminal domains, and folded or dynamic modules contribute to fiber strength, toughness, extensibility, damping, shape recovery, humidity stability, biodegradation, and recyclability. We further connect these sequence–structure–property relationships to applications in structural textiles, biomedical fibers, smart and protective systems, and sustainable materials. Finally, we discuss future opportunities in scalable recombinant production and data-driven sequence design. These advances are expected to accelerate the translation of engineered protein fibers into practical high-performance materials.