Synthetic Biology-based Construction of Unnatural Perylenequinones with Improved Photodynamic Anticancer Activities.

The construction of structural complexity and diversity of natural products is crucial for drug discovery and development. To overcome high dark toxicity and poor photostability of natural photosensitizer perylenequinones (PQs) for photodynamic therapy, herein, we aim to introduce the structural complexity and diversity to biosynthesize the desired unnatural PQs in fungus Cercospora through synthetic biology-based strategy. Thus, we first elucidate the intricate biosynthetic pathways of class B PQs and reveal how the branching enzymes create their structural complexity and diversity from a common ancestor. This enables the rational reprogramming of cercosporin biosynthetic pathway in Cercospora to generate diverse unnatural PQs without chemical modification. Among them, unnatural cercosporin A displays remarkably low dark toxicity and high photostability with retention of great photodynamic anticancer and antimicrobial activities. Moreover, it is found that, unlike cercosporin, unnatural cercosporin A could be selectively accumulated in cancer cells, providing potential targets for drug development. Therefore, this work provides a comprehensive foundation for preparing unnatural products with customized functions through synthetic biology-based strategies, thus facilitating drug discovery pipelines from nature.

Evaluating the Potential Safety Risk of Plant-Based Meat Analogues by Analyzing Microbial Community Composition.

Plant-based meat analogues offer an environmentally and scientifically sustainable option as a substitute for animal-derived meat. They contribute to reducing greenhouse gas emissions, freshwater consumption, and the potential risks associated with zoonotic diseases linked to livestock production. However, specific processing methods such as extrusion or cooking, using various raw materials, can influence the survival and growth of spoilage and pathogenic microorganisms, resulting in differences between plant-based meat analogues and animal meat. In this study, the microbial communities in five different types of plant-based meat analogues were investigated using high-throughput sequencing. The findings revealed a diverse range of bacteria, including Cyanobacteria, Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, and Chloroflexi, as well as fungi such as Ascomycota, Basidiomycota, Phragmoplastophyta, Vertebrata, and Mucoromycota. Additionally, this study analyzed microbial diversity at the genus level and employed phenotype prediction to evaluate the relative abundance of various bacterium types, including Gram-positive and Gram-negative bacteria, aerobic, anaerobic, and facultative anaerobic bacteria, as well as potential pathogenic bacteria. The insights gained from this study provide valuable information regarding the microbial communities and phenotypes of different plant-based meat analogues, which could help identify effective storage strategies to extend the shelf-life of these products.