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Bacterial endophytes dwelling in medicinal plants represent an as yet underexplored source of bioactive natural products with the potential to be developed into drugs against various human diseases. For the first time, several Streptomyces spp. were isolated from the rare and endangered traditional medicinal plant Leontopodium nivale ssp. alpinum, also known as Edelweiss. In the search for novel natural products, nine endophytic Streptomyces spp. from Edelweiss were investigated via genome sequencing and analysis, followed by fermentation in different media and investigation of secondary metabolomes. A total of 214 secondary metabolite biosynthetic gene clusters (BGCs), of which 35 are presumably unique, were identified by the bioinformatics tool antiSMASH in the genomes of these isolates. LC-MS analyses of the secondary metabolomes of these isolates revealed their potential to produce both known and presumably novel secondary metabolites, whereby most of the identified molecules could be linked to their cognate BGCs. This work sets the stage for further investigation of endophytic streptomycetes from Edelweiss aimed at the discovery and characterization of novel bioactive natural products. [ABSTRACT FROM AUTHOR]

Among the plant‐associated microorganisms, the so‐called endophytes continue to attract much attention because of their ability not only to protect host plants from biotic and abiotic stress factors, but also the potential to produce bioactive secondary metabolites. The latter property can elicit growth‐promoting effects on plants, as well as boost the production of plant‐specific secondary metabolites with valuable pharmacological properties. In addition, endophyte‐derived secondary metabolites may be a rich source for the discovery of drugs to treat various diseases, including infections and cancer. However, the full potential of endophytes to produce bioactive secondary metabolites is often not revealed upon conventional cultivation in the laboratory. New advances in genomics and metabolic engineering offer exciting opportunities for the exploration and exploitation of endophytes' biosynthetic potential. This review focuses on bacterial endophytes of medicinal plants, some of their secondary metabolites and recent advances in deciphering their biosynthesis. The latter may assist in genetic engineering efforts aimed at the discovery of novel bioactive compounds with the potential to be developed into drugs. [ABSTRACT FROM AUTHOR]

Six putative regulatory genes are located at the flank of the nystatin biosynthetic gene cluster in Streptomyces noursei ATCC 11455. Gene inactivation and complementation experiments revealed that nysRI, nysRII, nysRIII, and nysRIV are necessary for efficient nystatin production, whereas no significant roles could be demonstrated for the other two regulatory genes. To determine the in vivo targets for the NysR regulators, chromosomal integration vectors with the xylE reporter gene under the control of seven putative promoter regions upstream of the nystatin structural and regulatory genes were constructed. Expression analyses of the resulting vectors in the S. noursei wild-type strain and regulatory mutants revealed that the four regulators differentially affect certain promoters. According to these analyses, genes responsible for initiation of nystatin biosynthesis and antibiotic transport were the major targets for regulation. Data from cross-complementation experiments showed that nysR genes could in some cases substitute for each other, suggesting a functional hierarchy of the regulators and implying a cascade-like mechanism of regulation of nystatin biosynthesis.

A new methyl-specific restriction system (MSR) was identified in Streptomyes lividans after it was conjugated with S. bambergiensis and pBL2 was transferred. When the genetically detected pBL2 and the physically detected pBL2.1 elements are present in S. lividans, a previously unknown MSR system is detected. Therefore, either these elements carry a gene for MSR, of which there is only one known case, or they activate a MSR system that has been dormant in S. lividans.

The culture broth of endophytic Streptomyces sp. AB100, isolated from the shoots of medicinal plant Atropa belladonna (L.) was investigated for the presence of antibacterial compounds. After initial testing followed by bioactivity-guided fractionation, six new piperazic acid (PA)-containing congeners of two known peptides, JBIR-39 and JBIR-40, were identified by HR-MS/MS and NMR analyses. Only the dehydroxylated hexapeptidic derivatives with unusual incorporation of four PA moieties exhibited weak antibacterial activity against Gram-positive test organism Bacillus subtilis. A 16S rDNA-based phylogenetic tree of known Streptomyces spp. producing PA-containing hexapeptides isolated from different habitats and endophyte Streptomyces AB100 showed considerable diversity, suggesting that these metabolites may play an important environmental role beyond their antibacterial activity. [ABSTRACT FROM AUTHOR]

The identification, isolation and analysis of the new thiopeptide antibiotic, TP-1161, biosynthetic gene cluster from Nocardiopsis is described. The attempts at heterologous expression of the TP-1161 gene cluster in Streptomyces coelicolor have failed, but its identity is confirmed through the targeted gene inactivation in the original host.

Marine sediment-derived actinomycete isolates are studied for the production of antimicrobial secondary metabolites by using microwell plate fermentations and a range of media and conditions. The isolation and structural and biological characterization of a new thiopeptide antibiotic, designated as TP-1161, produced by a marine sediment-derived Nocardiopsis isolate is described.

The cloning and sequencing of a new macrolactam biosynthetic gene cluster ML-449 with high similarity to the 20-membered macrolactam BE-14106 gene cluster is described. The comparison of the ML-449, BE-14106, vicenistatin and salinilactam biosynthetic gene clusters has shown an evolutionary relationship between them and has provided insights into the processes governing the evolution of small-ring macrolactam biosynthesis.