Proximity-Guaranteed DNA Machine for Accurate Identification of Breast Cancer Extracellular Vesicles.

Breast cancer is one of the most diagnosed cancers worldwide. Precise diagnosis and subtyping have important significance for targeted therapy and prognosis prediction of breast cancer. Herein, we design a proximity-guaranteed DNA machine for accurate identification of breast cancer extracellular vesicles (EVs), which is beneficial to explore the subtype features of breast cancer. In our design, two proximity probes are located close on the same EV through specific recognition of coexisting surface biomarkers, thus being ligated with the help of click chemistry. Then, the ligated product initiates the operation of a DNA machine involving catalytic hairpin assembly and clusters of regularly interspaced short palindromic repeats (CRISPR)-Cas12a-mediated trans-cleavage, which finally generates a significant response that enables the identification of EVs expressing both biomarkers. Principle-of-proof studies are performed using EVs derived from the breast cancer cell line BT474 as the models, confirming the high sensitivity and specificity of the DNA machine. When further applied to clinical samples, the DNA machine is shown to be capable of not only distinguishing breast cancer patients with special subtypes but also realizing the tumor staging regarding the disease progression. Therefore, our work may provide new insights into the subtype-based diagnosis of breast cancer as well as identification of more potential therapeutic targets in the future.

Application of functional peptides in the electrochemical and optical biosensing of cancer biomarkers.

Early screening and diagnosis are the most effective ways to prevent the occurrence and progression of cancers, thus many biosensing strategies have been developed to achieve economic, rapid, and effective detection of various cancer biomarkers. Recently, functional peptides have been gaining increasing attention in cancer-related biosensing due to their advantageous features of a simple structure, ease of synthesis and modification, high stability, and good biorecognition, self-assembly and antifouling capabilities. Functional peptides can not only act as recognition ligands or enzyme substrates for the selective identification of different cancer biomarkers but also function as interfacial materials or self-assembly units to improve the biosensing performances. In this review, we summarize the recent advances in functional peptide-based biosensing of cancer biomarkers according to the used techniques and the roles of peptides. Particular attention is focused on the use of electrochemical and optical techniques, both of which are the most commonly used techniques in the field of biosensing. The challenges and promising prospects of functional peptide-based biosensors in clinical diagnosis are also discussed.

FW0622, a new siderophore isolated from marine Verrucosispora sp. by genomic mining.

Using the draft genome sequence of Verrucosispora sp. FIM060022, we have identified a new desferrioxamine-like siderophore, FW0622. This is the first chemically characterized siderophore obtained from Verrucosispora. The structure was elucidated by extensive spectral analyses. The biosynthetic pathway of FW0622 was proposed to occur via the non-ribosomal peptide synthetase (NRPS)-independent (NIS) synthetase pathway based on the putative biosynthetic siderophore gene cluster in FIM060022. The results demonstrate that marine-derived Verrucosispora species deserve recognition as an important source of new natural products. Furthermore, this study verified that genome mining is an effective way to identify compounds that may be overlooked by traditional methods.

Draft Genome Sequence of Broad-Spectrum Antibiotic-Producing Marine Verrucosispora sp. Strain FIM060022.

Verrucosispora sp. strain FIM060022 shows multiple biological activities and produces polytype structure compounds, including abyssomicins, proximicin A, lumichrome, denosine, and desferrioxamine-like compounds. We present the draft genome sequence of the strain to help predict the biosynthesis of these compounds, identify further biosynthetic potential, and facilitate directed secondary metabolite production.