Tandem mass spectral metabolic profiling of 54 actinobacterial strains and their 459 mutants.

Natural 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.

Reversing the directionality of reactions between non-oxidative pentose phosphate pathway and glycolytic pathway boosts mycosporine-like amino acid production in Saccharomyces cerevisiae.

Background: Mycosporine-like amino acids (MAAs) are a class of strongly UV-absorbing compounds produced by cyanobacteria, algae and corals and are promising candidates for natural sunscreen components. Low MAA yields from natural sources, coupled with difficulties in culturing its native producers, have catalyzed synthetic biology-guided approaches to produce MAAs in tractable microbial hosts like Escherichia coli, Saccharomyces cerevisiae and Corynebacterium glutamicum. However, the MAA titres obtained in these hosts are still low, necessitating a thorough understanding of cellular factors regulating MAA production.

Application of Cas12j for Editing.

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.

Exploring a general multi-pronged activation strategy for natural product discovery in Actinomycetes.

Natural 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.

Transcriptomic and metabolomic characterization of antibacterial activity of .

Antibacterial 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 .

Natural Products from Singapore Soil-Derived Family and Evaluation of Their Biological Activities.

Natural 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.

Cost-effective hybrid long-short read assembly delineates alternative GC-rich hosts for natural product discovery.

With 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.

β-Cryptoxanthin Production in by Optimization of the Cytochrome P450 CYP97H1 Activity.

Cytochromes P450, forming a superfamily of monooxygenases containing heme as a cofactor, show great versatility in substrate specificity. Metabolic engineering can take advantage of this feature to unlock novel metabolic pathways. However, the cytochromes P450 often show difficulty being expressed in a heterologous chassis.

Cytochrome P450 Surface Domains Prevent the β-Carotene Monohydroxylase CYP97H1 of from Acting as a Dihydroxylase.

Molecular biodiversity results from branched metabolic pathways driven by enzymatic regioselectivities. An additional complexity occurs in metabolites with an internal structural symmetry, offering identical extremities to the enzymes. For example, in the terpene family, β-carotene presents two identical terminal closed-ring structures.

Antibacterial Thiopeptide GE2270-Congeners from .

Thiopeptides 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.

Chemical elicitation as an avenue for discovery of bioactive compounds from fungal endophytes.

The 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.

Antibacterial Spirotetronate Polyketides from an sp. Strain A30804.

Large 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.

Diethyl phthalate (DEP) perturbs nitrogen metabolism in Saccharomyces cerevisiae.

Phthalates 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.

Lipid accumulation facilitates mitotic slippage-induced adaptation to anti-mitotic drug treatment.

Aberrant 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.

Role of the serotonergic pathway in uterotonic activity of Ananas comosus (L.) Merr. - An in vitro and in vivo study.

Background: Ananas comosus (L.) Merr. has been used as a traditional medicine in inducing abortion in many countries.

Potent tocolytic activity of ethyl acetate fraction of Ananas comosus on rat and human uteri.

The aim of this study was to investigate the tocolytic properties of Ananas comosus extract in rat and human uterine tissue in vitro and in the rat in vivo. Organ bath technique was employed to perform functional studies in vitro. The PhysioTel transmitter was implanted in SD rats to measure the changes in intrauterine pressure (IUP) in vivo.

Isolation and Identification of an Anthracimycin Analogue from , a Halophile from a Saltern, by Genomic Mining Strategy.

Modern medicine is unthinkable without antibiotics; yet, growing issues with microbial drug resistance require intensified search for new active compounds. Natural products generated by Actinobacteria have been a rich source of candidate antibiotics, for example anthracimycin that, so far, is only known to be produced by species. Based on sequence similarity with the respective biosynthetic cluster, we sifted through available microbial genome data with the goal to find alternative anthracimycin-producing organisms.

Pyrrole carboxamidine tryptase inhibitors from Leptonychia pubescens.

The root and stem bark extracts of a Nigerian sample of Leptonychia pubescens Keay (Sterculiaceae) were found to inhibit the serine protease tryptase, a potential therapeutic target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Bioassay-guided isolation led to the identification of 1-beta-ribofuranosylbrunfelsamidine as the active component with a tryptase IC (50) of 3 microM. Brunfelsamidine was also isolated, but was only weakly active.