Metabolic Engineering of Corynebacterium glutamicum for the Production of Flavonoids and Stilbenoids.

Flavonoids and stilbenoids, crucial secondary metabolites abundant in plants and fungi, display diverse biological and pharmaceutical activities, including potent antioxidant, anti-inflammatory, and antimicrobial effects. However, conventional production methods, such as chemical synthesis and plant extraction, face challenges in sustainability and yield. Hence, there is a notable shift towards biological production using microorganisms like Escherichia coli and yeast. Yet, the drawbacks of using E. coli and yeast as hosts for these compounds persist. For instance, yeast's complex glycosylation profile can lead to intricate protein production scenarios, including hyperglycosylation issues. Consequently, Corynebacterium glutamicum emerges as a promising alternative, given its adaptability and recent advances in metabolic engineering. Although extensively used in biotechnological applications, the potential production of flavonoid and stilbenoid in engineered C. glutamicum remains largely untapped compared to E. coli. This review explores the potential of metabolic engineering in C. glutamicum for biosynthesis, highlighting its versatility as a cell factory and assessing optimization strategies for these pathways. Additionally, various metabolic engineering methods, including genomic editing and biosensors, and cofactor regeneration are evaluated, with a focus on C. glutamicum. Through comprehensive discussion, the review offers insights into future perspectives in production, aiding researchers and industry professionals in the field.

A novel finding of intra-genus inhibition of quorum sensing in Vibrio bacteria.

Quorum sensing is the process by which microbial cells sense and respond to the co-presence of others in their surrounding, through the detection of their autoinducers associated with gene expression regulation and thereby controlling many physiological processes, such as biofilm formation and/or bioluminescence, etc. In Vibrio bacteria, where quorum sensing is relatively well understood with three commonly known autoinducers (HAI-1, AI-2 and CAI-1), both intra-species and inter-species cell-cell communications occur but no inter-Vibrio-species quorum sensing inhibition has been reported. In this study, by screening bacterial isolated from soil and mud samples in a northern province in Vietnam, we discovered a strain that reduced more than 75% of the bioluminescence of a Vibrio harveyi, with evidence showing that such an inhibition might be associated with quorum sensing inhibition. The strain, designated as XTS1.2.9, was identified to be a Vibrio parahaemolyticus bacterium based on its morphological, physiological, biochemical and phylogenetic characteristics. We also tested XTS1.2.9 for its bioluminescence inhibition against different mutants lacking different quorum sensing autoinducers by using plate assays. The results showed that XTS1.2.9 inhibited the bioluminescence of the mutants having sensor 1, especially the one detecting CAI-1, and lacking sensor for AI-2; while it did not inhibit the mutants having only sensor for AI-2 and lacking sensor 1. Therefore, we propose an intra-genus quorum sensing inhibition mechanism involving CAI-1 to explain for such interactions between Vibrio parahaemolyticus and Vibrio harveyi. This phenomenon is reported for the first time and may have certain scientific and application implications.

Matrix metalloproteinases in Vietnamese patients with colorectal cancer.

Matrix metalloproteinases (MMPs), a family of endopeptidases also known as gelatinases, have been reported to affect the acquisition of the cell proliferative, cell invasive and metastatic phenotype of several types of cancer. In particular, the gelatinases MMP-2 and -9 have been revealed to facilitate tumor growth and invasion in patients with colorectal cancer (CRC). However, it is not known whether the gelatinase activity of MMP-2 and -9 is also elevated in Vietnamese patients with CRC. The activity of MMP-2 and -9 in the tissue samples of 103 patients with CRC was evaluated by gelatin zymography and quantified using ImageJ. The association between the level of activity of MMP-2 and -9 and various clinicopathological factors was analyzed, and Chisio BioPAX Editor software was used to visualize the biological pathways regulating the activity of the MMPs. The present study noticed significantly increased activity of active MMP-2 and MMP-9 in tumor tissues (P<0.01), and significantly decreased levels of pro-form MMP-2 and MMP-9 in tumor tissues (P<0.01), compared with that in adjacent tissues in patients with CRC. A correlation between the normalized different activity of MMP-2 and -9 and various clinicopathological features was observed. Furthermore, bioinformatics analysis indicated that the alteration in the activity of MMP-2 and MMP-9 may have been controlled by biological pathways involving the tissue inhibitors of metalloprotease-2 and -1. These findings indicate that the activity of the gelatinases MMP-2 and -9 affects the tumor progression and metastasis of patients with CRC, providing a potential novel approach for determining the prognosis of CRC.