Biosynthetic gene cluster profiling from North Java Sea Virgibacillus salarius reveals hidden potential metabolites.

Virgibacillus salarius 19.PP.SC1.6 is a coral symbiont isolated from Indonesia's North Java Sea; it has the ability to produce secondary metabolites that provide survival advantages and biological functions, such as ectoine, which is synthesized by an ectoine gene cluster. Apart from being an osmoprotectant for bacteria, ectoine is also known as a chemical chaperone with numerous biological activities such as maintaining protein stability, which makes ectoine in high demand in the market industry and makes it beneficial to investigate V. salarius ectoine. However, there has been no research on genome-based secondary metabolite and ectoine gene cluster characterization from Indonesian marine V. salarius. In this study, we performed a genomic analysis and ectoine identification of V. salarius. A high-quality draft genome with total size of 4.45 Mb and 4426 coding sequence (CDS) was characterized and then mapped into the Cluster of Orthologous Groups (COG) category. The genus Virgibacillus has an "open" pangenome type with total of 18 genomic islands inside the V. salarius 19.PP.SC1.6 genome. There were seven clusters of secondary metabolite-producing genes found, with a total of 80 genes classified as NRPS, PKS (type III), terpenes, and ectoine biosynthetic related genes. The ectoine gene cluster forms one operon consists of ectABC gene with 2190 bp gene cluster length, and is successfully characterized. The presence of ectoine in V. salarius was confirmed using UPLC-MS/MS operated in Multiple Reaction Monitoring (MRM) mode, which indicates that V. salarius has an intact ectoine gene clusters and is capable of producing ectoine as compatible solutes.

Sun protection and antibacterial activities of carotenoids from the soft coral Sinularia sp. symbiotic bacteria from Panjang Island, North Java Sea.

Carotenoids have shown beneficial applications in cosmetology, pharmacology, and medicine. However, environmental stress in the marine environment can trigger the production of unique secondary metabolites, such as carotenoids. These compounds can also be sustainably produced by symbiotic bacteria. We hypothesized that the soft corals in tropical regions may produce diverse biological secondary metabolites, including carotenoids, both by the host organism and their bacterial symbiont. The unique carotenoids may provide promising biological activity such as antioxidant, UV photoprotector, and antibacterial activities. To this end, we isolated and characterized the carotenoids isolated from the bacterial symbiont of Sinularia sp., a soft coral from Panjang Island, North Java Sea, strain 19. PP.Sc.13. Bacterial identification was performed using DNA barcoding of the 16S rRNA region. Identification of carotenoids was carried out using a spectrophotometer, High-Performance Liquid Chromatography (HPLC), and attenuated total reflection fourier-transformed infrared (ATR-FTIR) spectroscopy. The antioxidant activity was estimated using the diphenylpicrylhydrazyl (DPPH) method, while the Sun Protection Factor (SPF) and % transmission of erythema and pigmentation were determined based on colorimetric methods. The antibacterial activity assay was carried out using the agar diffusion method against two multidrug-resistant bacteria. The bacterial symbiont was identified as Virgibacillus sp. and the carotenoids isolated from this symbiont exhibited significant antioxidant activity and extra sun protection effect, thus categorized as UVA sunblock. Furthermore, the isolated carotenoids exhibited antibacterial activities against Methicillin Resistant-Staphylococcus aureus (MRSA) and Multidrug-resistant (MDR) Escherichia coli. This study provides evidence of the carotenoids produced by the soft coral bacterial symbiont Virgibacillus sp., which may be used as an antioxidant, sun protection, and antibacterial agent. Further investigation of the de novo biological production of carotenoids by Virgibacillus sp. is warranted.

Bixa orellana L. carotenoids: antiproliferative activity on human lung cancer, breast cancer, and cervical cancer cells in vitro.

Emerging evidence on the potential pro-oxidant effect of carotenoids provokes apoptosis of cancer cells. Bixa orellana L. is native to Central and South America, interestingly, is also cultivated worldwide. Apo-carotenoids present in B. orellana L. are mainly dominated by bixin and norbixin and demonstrate fundamental antioxidant activity. Anti-proliferative activity on human cancer cells is rarely investigated. We isolated bixin from B. orellana L. found in the island of Java using Ultra-Fast Liquid Chromatography and confirmed the isolated compound using Liquid Chromatography-MS/MS. Bixin and crude extract were examined on human lung cancer (A549), cervical cancer (HeLa), and breast cancer (MCF-7). Anti-proliferative activity revealed to be promising on both, the isolated pigment and crude extract. Further investigation on the mechanism of action and effect on other cell lines, both in vitro and in vivo, are required before clinical translation.

Bixin and fucoxanthin sensitize human lung cancer and cervical cancer cell to cisplatin in vitro.

OBJECTIVE: Cisplatin is a conventional anticancer drug that generates reactive oxygen species and causes apoptosis. However, many cancer cells develop alterations in the ATP binding cassette transporter responsible for the uptake and efflux process, which leads to resistance. Many natural products have shown potential to compete with ATP binding cassette transporter and may sensitize resistant cells to cisplatin. Studies have shown pro-oxidant effect of carotenoids that promote apoptosis of cancer cells. Bixin and fucoxanthin are well-known carotenoids with known antioxidant properties, however their bioactivity in lung cancer cells, clinically known to develop resistance due to ATP binding cassette transporter, has been minimally studied. This study is the first to investigate the potential of bixin and fucoxanthin to sensitize human lung cancer cell line, A549 and cervical cancer cell line, HeLa, to cisplatin. Drug combination method developed by Chou and Talalay theorem was employed. RESULT: Employing the best combination ratio, this study shows selective sensitization of cancer cells to cisplatin after bixin and fucoxanthin treatment. Further study on the mechanism of action in specific types of cancer cells is warranted. It may improve cisplatin sensitivity in tumors and rational use of cancer drugs.