A key factor influencing consumer acceptance of soybean products is the aroma and taste profile, which can be modulated through fermentation using unique microbial strains. This study aimed to identify and characterize novel microbial strains with the potential to enhance flavour profiles including umami, while reducing undesirable flavour notes such as beany aromas. The results showed an 800% (8-fold) increase in free amino acids in samples fermented with , which correlated with an increase in umami intensity as measured using an E-tongue.
View Article and Find Full Text PDFNatural products encompass a diverse range of compounds with high impact applications in consumer care, agriculture and most notably, therapeutics. However, despite the expansive chemical repertoire indicated in genomic information of microbes, only a small subset can be obtained under laboratory conditions. To increase accessible chemical space and realize Nature's full chemical potential, a multi-pronged genetic- and cultivation-based strategy has been employed to activate and upregulate natural product biosyntheses in native and heterologous strains.
View Article and Find Full Text PDFMicrob Cell Fact
May 2024
In recent years, CRISPR-Cas toolboxes for editing have rapidly accelerated natural product discovery and engineering. However, Cas efficiencies are oftentimes strain-dependent, and the commonly used Cas9 (SpCas9) is notorious for having high levels of off-target toxicity effects. Thus, a variety of Cas proteins is required for greater flexibility of genetic manipulation within a wider range of strains.
View Article and Find Full Text PDFNatural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria.
View Article and Find Full Text PDFAntibacterial resistance poses a significant global threat, necessitating the discovery of new therapeutic agents. Plants are a valuable source of secondary metabolites with demonstrated anticancer and antibacterial properties. In this study, we reveal that exhibits both bacteriostatic and bactericidal effects against and .
View Article and Find Full Text PDFNatural products have long been used as a source of antimicrobial agents against various microorganisms. Actinobacteria are a group of bacteria best known to produce a wide variety of bioactive secondary metabolites, including many antimicrobial agents. In this study, four actinobacterial strains found in Singapore terrestrial soil were investigated as potential sources of new antimicrobial compounds.
View Article and Find Full Text PDFThe use of solid lipid sidestreams have been overlooked as a feedstock for the production of microbial biomass for food and feed applications and little to no recent work has examined the utilization of solid fatty acid distillates (FADs), which are a significant residue from vegetable oil processing. Yarrowia lipolytica and Rhodosporidium toruloides cultivated on cocoa fatty acid distillates (CFAD) generated final cell dry weight values > 40 g/L, with strong productivity (3.3 g/L·h) and rich protein (>45%) and lipid content (>25%).
View Article and Find Full Text PDFWith the advent of rapid automated identification of biosynthetic gene clusters (BGCs), genomics presents vast opportunities to accelerate natural product (NP) discovery. However, prolific NP producers, , are exceptionally GC-rich (>80%) and highly repetitive within BGCs. These pose challenges in sequencing and high-quality genome assembly which are currently circumvented intensive sequencing.
View Article and Find Full Text PDFAdaptation to a wide variety of habitats allows fungi to develop unique abilities to produce diverse secondary metabolites with diverse bioactivities. In this study, 30 fungi isolated from St. John's Island, Singapore were investigated for their general biosynthetic potential and their ability to produce antimicrobial secondary metabolites (SMs).
View Article and Find Full Text PDFThiopeptides are macrocyclic natural products with potent bioactivity. Nine new natural thiopeptides (1−9) were obtained from a Nonomuraea jiangxiensis isolated from a terrestrial soil sample collected in Singapore. Even though some of these compounds were previously synthesized or isolated from engineered strains, herein we report the unprecedented isolation of these thiopeptides from a native Nonomuraea jiangxiensis.
View Article and Find Full Text PDFThe present study investigated the molecular phylogeny, antimicrobial and cytotoxic activities of fungal endophytes obtained from the A*STAR Natural Organism Library (NOL) and previously isolated from Sungei Buloh Wetland Reserve, Singapore. Phylogenetic analysis based on ITS2 gene suggests that these isolates belong to 46 morphotypes and are affiliated to 23 different taxa in 17 genera of the phylum. was the most dominant fungal genus accounting for 37% of all the isolates, followed by (13%), (10.
View Article and Find Full Text PDFLarge scale cultivation and chemical investigation of an extract obtained from sp. resulted in the identification of six previously undescribed spirotetronates (pyrrolosporin B and decatromicins C-G; -), along with six known congeners, namely decatromicins A-B (-), BE-45722B-D (-), and pyrrolosporin A (). The chemical structures of compounds - were characterized via comparison with previously reported data and analysis of 1D/2D NMR and MS data.
View Article and Find Full Text PDFis a genus of ascomycetous fungi within the family . Members of this genus have been isolated as endophytes from a wide range of host plants and also from plant debris within terrestrial and marine habitats, where they are thought to function as saprobes. sp.
View Article and Find Full Text PDFEndophytic microorganisms are an important source of bioactive secondary metabolites. In this study, fungal endophytes obtained from A*STAR's Natural Product Library (NPL) and previously isolated from different habitats of Singapore were investigated for their diversity, antimicrobial, and cytotoxic activities. A total of 222 fungal strains were identified on the basis of sequence analysis of ITS region of the rDNA gene.
View Article and Find Full Text PDFPhthalates are ubiquitously used as plasticizers in various consumer care products. Diethyl phthalate (DEP), one of the main phthalates, elicits developmental and reproductive toxicities but the underlying mechanisms are not fully understood. Chemogenomic profiling of DEP in S.
View Article and Find Full Text PDFSortase A (SrtA) is a membrane-associated enzyme that anchors surface-exposed proteins to the cell wall envelope of Gram-positive bacteria such as . As SrtA is essential for Gram-positive bacterial pathogenesis but dispensable for microbial growth or viability, SrtA is considered a favorable target for the enhancement of novel anti-infective drugs that aim to interfere with key bacterial virulence mechanisms, such as biofilm formation, without developing drug resistance. Here, we used virtual screening to search an in-house natural compound library and identified two natural compounds, N1287 (Skyrin) and N2576 ((4,5-dichloro-1H-pyrrol-2-yl)-[2,4-dihydroxy-3-(4-methyl-pentyl)-phenyl]-methanone) that inhibited the enzymatic activity of SrtA.
View Article and Find Full Text PDFNotonesomycin A is a 32-membered bioactive glycosylated macrolactone known to be produced by Streptomyces aminophilus subsp. notonesogenes 647-AV1 and S. aminophilus DSM 40186.
View Article and Find Full Text PDFSUGCT (C7orf10) is a mitochondrial enzyme that synthesizes glutaryl-CoA from glutarate in tryptophan and lysine catabolism, but it has not been studied in vivo. Although mutations in Sugct lead to Glutaric Aciduria Type 3 disease in humans, patients remain largely asymptomatic despite high levels of glutarate in the urine. To study the disease mechanism, we generated SugctKO mice and uncovered imbalanced lipid and acylcarnitine metabolism in kidney in addition to changes in the gut microbiome.
View Article and Find Full Text PDFBackground & Aims: Some oncogenes encode transcription factors, but few drugs have been successfully developed to block their activity specifically in cancer cells. The transcription factor SALL4 is aberrantly expressed in solid tumor and leukemia cells. We developed a screen to identify compounds that reduce the viability of liver cancer cells that express high levels of SALL4, and we investigated their mechanisms.
View Article and Find Full Text PDFBackground: Phomafungin is a recently reported broad spectrum antifungal compound but its biosynthetic pathway is unknown. We combed publicly available Phoma genomes but failed to find any putative biosynthetic gene cluster that could account for its biosynthesis.
Results: Therefore, we sequenced the genome of one of our Phoma strains (F3723) previously identified as having antifungal activity in a high-throughput screen.
We have isolated Hypoculoside, a new glycosidic amino alcohol lipid from the fungus Acremonium sp. F2434 belonging to the order Hypocreales and determined its structure by 2D-NMR (Nuclear Magnetic Resonance) spectroscopy. Hypoculoside has antifungal, antibacterial and cytotoxic activities.
View Article and Find Full Text PDFAberrant lipid accumulation is a hallmark of cancer known to contribute to its aggressiveness and malignancy. Emerging studies have demonstrated context-dependent changes in lipid metabolism during chemotherapy. However, there is little known regarding the mechanisms linking lipid metabolism to chemotherapy-induced cell fates.
View Article and Find Full Text PDF