The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a major threat for human health. In recent years, genome sequencing has unveiled many poorly expressed antibiotic clusters in actinomycetes. Here, we report well-defined ecological collection >800 actinomycetes obtained from sites the Himalaya and Qinling mountains, used these concept study to see how efficiently antibiotics can be elicited against MDR isolated recently clinic. Using 40 different growth conditions,...

Actinomycetes and filamentous fungi produce a wide range of bioactive compounds, with applications as antimicrobials, anticancer agents or agrochemicals. Their genomes contain far larger number gene clusters for natural products than originally anticipated, novel approaches are required to exploit this potential reservoir new drugs. Here, we show that co-cultivation the model microbes Streptomyces coelicolor Aspergillus niger has major impact on their secondary metabolism. NMR-based...

Actinomycetes are a major source of antimicrobials, anticancer compounds, and other medically important products, their genomes harbor extensive biosynthetic potential. Major challenges in the screening these microorganisms to activate expression cryptic gene clusters development technologies for efficient dereplication known molecules. Here we report identification previously unidentified isatin-type antibiotic produced by Streptomyces sp. MBT28, following strategy based on NMR-based...

Myxobacteria are fascinating prokaryotes featuring a potent capacity for producing wealth of bioactive molecules with intricate chemical topology as well intriguing enzymology, and thus it is critical to developing an efficient pipeline bioprospecting. Herein, we construct the database MyxoDB, first public compendium solely dedicated myxobacteria, which enabled us provide overview structural diversity taxonomic distribution known myxobacterial natural products. Moreover, demonstrated that...

This review presents a comprehensive overview of recent advances in the discovery methodologies, new structures, bioactivities, and unique biosynthetic logics myxobacterial natural products reported from January 2017 to November 2023.

Actinomycetes produce the majority of antibiotics currently in clinical use. The efficiency antibiotic production is affected by multiple factors such as nutrients, pH, temperature and growth phase. Finding optimal harvesting time crucial for successful isolation desired bioactive metabolites from actinomycetes, but this conventional chemical analysis has limitations due to metabolic complexity.This study explores utility NMR-based metabolomics (1) optimizing fermentation known and/or...

Mining of microbial genomes has revealed that actinomycetes harbor far more biosynthetic potential for bioactive natural products than anticipated. Activation (cryptic) gene clusters and identification the corresponding metabolites become a focal point drug discovery. Here, we applied NMR-based metabolomics combined with bioinformatics to identify novel C-glycosylpyranonaphthoquinones in Streptomyces sp. MBT76 elucidate pathway. Following activation cryptic qin cluster type II polyketide...

Glycodiversification can optimize the properties of pharmaceutical compounds, and versatile glycosyltransferases (GTs) are key enzymatic toolkits to achieve this goal. Plant GTs in GT1 family (GT1-pGTs) have attracted much attention due their promising substrate promiscuity, but previous investigations on GT1-pGTs were mainly conducted sporadically without systematic phylogenetic comparisons. In study, we exemplified phylogeny-guided characterization highly promiscuous from contemporary...

Myxobacteria are a prolific source of secondary metabolites with sheer chemical complexity, intriguing biosynthetic enzymology, and diverse biological activities. In this study, we report the discovery, biosynthesis, biomimetic total synthesis, physiological function, structure–activity relationship, self-resistance mechanism 5-methylated pyrazinone coralinone from myxobacterium Corallococcus exiguus SDU70. A single NRPS/PKS gene corA was genetically biochemically demonstrated to orchestrate...

The increasing bacterial multidrug resistance necessitates novel drug-discovery efforts. One way to obtain chemistry is glycosylation, which prevalent in nature, with high diversity both the sugar moieties and targeted aglycones. Kitasatospora sp. MBT66 produces endophenaside antibiotics, a family of (methyl-)rhamnosylated phenazines. Here we show that this strain also plecomacrolide leucanicidin (1), derived from bafilomycin A1 by glycosylation same methyl-rhamnosyl moiety as present...

The explosive increase in genome sequencing and the advances bioinformatic tools have revolutionized rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters potential to specify many yet unknown bioactive specialized metabolites, representing a huge unexploited pool of chemical diversity. Here, we describe novel group catecholate–hydroxamate siderophores termed qinichelins (2–5) Streptomyces...

Actinobacteria are a major source of novel bioactive natural products. A challenge in the screening these microorganisms lies finding favorable growth conditions for secondary metabolite production and dereplication known molecules. Here, we report that Streptomyces sp. MBT27 produces 4-quinazolinone alkaloids response to elevated levels glycerol, whereby quinazolinones (1) B (2) form new sub-class this interesting family Global Natural Product Social molecular networking (GNPS) resulted...

An unprecedented 19-membered allenic macrolide archangiumide (1) was discovered from the myxobacterium Archangium violaceum SDU8 by integrating NMR-based metabolic profiling and genome mining. Its biosynthesis pathway proposed based on architectural analysis of encoding trans-AT PKS genes validated isotope labeling. The methodology combing 2D bioinformatics-aided structure prediction, as exemplified this study, is anticipated to improve discovery efficiency a broader range microbial "dark matter".

There is a continuous need for novel microbial natural products to fill the drying-up drug development pipeline. Herein, we report myxadazoles from Myxococcus sp. SDU36, family of chimeric small molecules that consist N-ribityl 5,6-dimethylbenzimidazole and linear fatty acid chain endowed with an isoxazole ring. The experiments genome sequencing, gene insertion mutation, isotope labelling, precursor feeding demonstrated was encoded by non-canonical PKS/NRPS cluster, whereas origin related...

Genome mining has revealed that myxobacteria contain a myriad of cryptic biosynthetic gene clusters (BGCs). Here, we report the characterization panel myxobacterial promoters with variable strength are applicable in engineering BGCs myxobacteria. The screened strongest constitutive promoter was used to efficiently enhance expression two complex governing biosynthesis myxochromide and DKxanthene model myxobacterium Myxococcus xanthus DK1622. We also showcased combination MS2-based spectral...

Abstract Glycosyltransferases typically display acceptor substrate flexibility but more stringent donor specificity. BsGT-1 is a highly effective glycosyltransferase to glycosylate macrolides, including epothilones, promising antitumor compounds. Here, we show that has three major regions significantly influencing the glycodiversification of epothilone B based on structural molecular docking, “hot spots” alanine scanning, and site saturation mutagenesis. Mutations in PSPG-like motif region...

Angucyclines are type II polyketide natural products, often characterized by unusual structural rearrangements through B- or C-ring cleavage of their tetracyclic backbone. While the enzymes involved in B-ring have been extensively studied, little is known leading to cleavage. Here, we unravel function oxygenases biosynthesis lugdunomycin, a highly rearranged cleaved angucycline derivative. Targeted deletion oxygenase genes, combination with molecular networking and elucidation, showed that...

The alcohol dehydrogenase (ADH) system plays a critical role in sugar metabolism involving not only ethanol formation and consumption but also the general "cofactor balance" mechanism. Candida maltosa is able to ferment glucose as well xylose produce significant amount of ethanol. Here we report ADH C. composed three microbial group I genes (CmADH1, CmADH2A CmADH2B), mainly focusing on its metabolic regulation physiological function.Genetic analysis indicated that CmADH2B tandemly located...

The biosynthesis of aromatic polyketides derived from type II polyketide synthases (PKSs) is complex, and it not uncommon that highly similar gene clusters give rise to diverse structural architectures. act biosynthetic cluster (BGC) the model actinomycete Streptomyces coelicolor A3(2) an archetypal PKS. Here we show BGC also specifies GTRI-02 (1) propose a mechanism for biogenesis its 3,4-dihydronaphthalen-1(2H)-one backbone. Polyketide 1 was produced by sp. MBT76 after activation act-like...