Streptomyces

Phytopathogenic fungi Alternaria alternata and Colletotrichum gloeosporioides cause diseases in plant tissues as well as significant postharvest losses. The use of chemical fungicides for their control has negative effects on health and the environment. Secondary metabolites from halophilic bacteria are a promising alternative for new antifungal compounds. In the present study, halophilic bacteria were isolated and characterized from two sites with saline soils called branquizales in Campeche, Mexico. A total of 64 bacteria were isolated...

Single-stranded DNA-binding proteins (SSB) are crucial in DNA metabolism. While Escherichia coli SSB is extensively studied, the significance of its C-terminal domain has only recently emerged. This study explored the significance of C-domains of two paralogous Ssb proteins in S. coelicolor. Mutational analyses of C-domains uncovered a novel role of SsbA during sporulation-specific cell division and demonstrated that the C-tip is non-essential for survival. In vitro methods revealed altered biophysical and biochemical properties of Ssb proteins with modified C-domains...

Flavonoids exhibit various bioactivities including anti-oxidant, anti-tumor, anti-inflammatory, and anti-viral properties. Methylated flavonoids are particularly significant due to their enhanced oral bioavailability, improved intestinal absorption, and greater stability. The heterologous production of plant flavonoids in bacterial factories involves the need for enough biosynthetic precursors to allow for high production levels. These biosynthetic precursors are malonyl-CoA and l-tyrosine. In this work, to enhance flavonoid biosynthesis in Streptomyces albidoflavus , we conducted a transcriptomics study for the identification of candidate genes involved in l-tyrosine catabolism...

Bis (3',5')-cyclic diguanylic acid (c-di-GMP) is a ubiquitous second messenger that controls several metabolic pathways in bacteria. In Streptomyces , c-di-GMP is associated with morphological differentiation, which is related to secondary metabolite production. In this study, we identified and characterized a diguanylate cyclase (DGC), CdgB, from Streptomyces diastatochromogenes 1628, which may be involved in c-di-GMP synthesis, through genetic and biochemical analyses. To further investigate the role of CdgB, the cdgB -deleted mutant strain Δ- cdgB and the cdgB -overexpressing mutant strain O- cdgB were constructed by genetic engineering...

We report the discovery of a novel cyclic nonribosomal peptide (NRP), acyl-surugamide A2, from a marine-derived Streptomyces albidoflavus RKJM-0023 (CP133227). The structure of acyl-surugamide A2 was elucidated using a combination of NMR spectroscopy, MS2 fragmentation analysis, and comparative analysis of the sur biosynthetic gene cluster. Acyl-surugamide A2 contains all eight core amino acids of surugamide A, with a modified N-ε-acetyl-L-lysine residue. Our study highlights the potential of marine Streptomyces strains to produce novel natural products with potential therapeutic applications...

Isatropolone C from Streptomyces sp. CPCC 204095 features a fused cyclopentadienone-tropolone-oxacyclohexadiene tricyclic moiety in its structure. Herein, we report an isatropolone C dimer derivative, di-isatropolone C, formed spontaneously from isatropolone C in methanol. Notably, the structure of di-isatropolone C resolved by NMR reveals a newly formed cyclopentane ring to associate the two isatropolone C monomers. The configurations of four chiral carbons, including a ketal one, in the cyclopentane ring are assigned using quantum NMR calculations and DP4+ probability...

The Streptomyces strain G222, isolated from a Vietnamese marine sediment, was confidently identified by 16 S rRNA gene sequencing. Its AcOEt crude extract was successfully analyzed using non-targeted LC-MS/MS analysis, and molecular networking, leading to a putative annotation of its chemical diversity thanks to spectral libraries from GNPS and in silico metabolite structure prediction obtained from SIRIUS combined with the bioinformatics tool conCISE (Consensus Annotation Propagation of in silico Elucidations)...

Streptomyces has the largest repertoire of natural product biosynthetic gene clusters (BGCs), yet developing a universal engineering strategy for each Streptomyces species is challenging. Given that some Streptomyces species have larger BGC repertoires than others, we proposed that a set of genes co-evolved with BGCs to support biosynthetic proficiency must exist in those strains, and that their identification may provide universal strategies to improve the productivity of other strains. We show here that genes co-evolved with natural product BGCs in Streptomyces can be identified by phylogenomics analysis...

UNLABELLED: In most actinomycetes, GlnR governs both nitrogen and non-nitrogen metabolisms (e.g., carbon, phosphate, and secondary metabolisms). Although GlnR has been recognized as a global regulator, its regulatory role in central carbon metabolism [e.g., glycolysis, gluconeogenesis, and the tricarboxylic acid (TCA) cycle] is largely unknown. In this study, we characterized GlnR as a direct transcriptional repressor of the pckA gene that encodes phosphoenolpyruvate carboxykinase, catalyzing the conversion of the TCA cycle intermediate oxaloacetate to phosphoenolpyruvate, a key step in gluconeogenesis...

Mollemycin A (MOMA) is a unique glyco-hexadepsipeptide-polyketide that was isolated from a Streptomyces sp. derived from the Australian marine environment. MOMA exhibits remarkable inhibitory activity against both drug-sensitive and multidrug-resistant malaria parasites. Optimizing MOMA through structural modifications or product enhancements is necessary for the development of effective analogues. However, modifying MOMA using chemical approaches is challenging, and the production titer of MOMA in the wild-type strain is low...

Aromadendrin and taxifolin are two flavanonols (derived from the precursor naringenin) displaying diverse beneficial properties for humans. The carbon skeleton of these flavonoids may be transformed by the human gastrointestinal microbiota into other compounds, like auronols, which exert different and interesting biological activities. While research in flavonoids has become a certainly extensive field, studies about auronols are still scarce. In this work, different versions of the key plant enzyme for flavanonols biosynthesis, The flavanone 3-hydroxylase (F3H), has been screened for selecting the best one for the de novo production of these compounds in the bacterial factory Streptomyces albidoflavus UO-FLAV-004-NAR, a naringenin overproducer strain...

Increasing evidence infers that some complex diseases are attributed to co-infection with multiple pathogens, such as shrimp white feces syndrome (WFS); however, there is a lack of experimental evidence to validate such causal link. This deficiency further impedes rational design of probiotics to elicit desired benefits to shrimp WFS resistance. Herein, we validated the causal roles of Vibrio fluvialis, V. coralliilyticus and V. tubiashii (in a ratio of 7:2:1) in shrimp WFS etiology, which fully satisfied Koch's postulates...

Tricholoma bakamatsutake is a delicious and nutritious ectomycorrhizal fungus. However, its cultivation is hindered owing to limited studies on its symbiotic relationships. The symbiotic relationship between T. bakamatsutake and its host is closely related to the shiro, a complex network composed of mycelium, mycorrhizal roots, and surrounding soil. To explore the symbiotic relationship between T. bakamatsutake and its host, soil samples were collected from T. bakamatsutake shiro (Tb) and corresponding Q. mongolica rhizosphere (CK) in four cities in Liaoning Province, China...

Spinosad is a potent insecticide produced by Saccharopolyspora spinosa . However, it harbors certain limitations of a low growing rate and unfeasible genetic manipulation that can be overcome by adopting a superior platform, such as Streptomyces . Herein, we exploited the industrial tylosin-producing Streptomyces fradiae J1-021 for the heterologous production of spinosad. An engineered strain (HW01) with deletion of the tylosin biosynthetic gene cluster (BGC) was constructed and then transformed with the natural spinosad BGC...

This study aimed to isolate actinomycetes that exhibit strong herbicidal activity, identify compounds active against weeds, and researching methods to improve the production of these compounds through culture optimization to establish a foundation for the development of environmentally friendly bioherbicides. 334-W4, one of the herbicidal active substances isolated from the culture broth of Streptomyces sp. KRA16-334, exhibited herbicidal activity against various weeds. The molecular formula of 334-W4 was determined to be C16H26N2O6, based on ESI-MS (m/z) and 1H and 13C NMR spectral data...

Cinnamoyl moiety containing nonribosomal peptides represented by pepticinnamin E are a growing family of natural products isolated from different Streptomyces species and possess diverse bioactivities. The soil bacterium Streptomyces mirabilis P8-A2 harbors a cryptic pepticinnamin biosynthetic gene cluster, producing azodyrecins as major products. Inactivation of the azodyrecin biosynthetic gene cluster by CRISPR-BEST base editing led to the activation and production of pepticinnamin E ( 1 ) and its analogues, pepticinnamins N, O, and P ( 2 - 4 ), the structures of which were determined by detailed NMR spectroscopy, HRMS data, and Marfey's reactions...

Drought is a major obstacle to the development of naked oat industry. This work investigated mechanisms by which exogenous Streptomyces albidoflavus T4 and Streptomyces rochei D74 improved drought tolerance in naked oat (Avena nuda ) seedlings. Results showed that in the seed germination experiment, germination rate, radicle and hypocotyl length of naked oat seeds treated with the fermentation filtrate of T4 or D74 under PEG induced drought stress increased significantly. In the hydroponic experiment, the shoot and root dry weights of oat seedlings increased significantly when treated with the T4 or D74 fermentation filtrate under the 15% PEG induced drought stress (S15)...

Plant growth regulators (PGRs) play an important role in alleviating the detrimental effects of biotic and abiotic stress and improving crop yield and quality. As a novel PGR from Streptomyces registered in 2021, guvermectin (GV) has the potential to improve plant yield and defense, making its application in agriculture a subject of interest. Here, we describe the discovery process, functional activities, agricultural applications, toxicity, environmental safety, and biosynthetic mechanism of GV. This Perspective provides a guide for the development of novel PGRs from microorganisms...

Gamma-aminobutyric acid (GABA) is an amino acid that has a role as a signaling molecule. In plants, its involvement in stress responses is widely investigated. A newly developed method of quantification of GABA is described in this chapter. The assay kit consisting of three bacterial enzymes enables easy but accurate measurement of GABA (~200 mg/mL) based on the serial enzymatic reaction leading to dye formation. The method was successfully applied to measure the GABA content in several plant tissues.

In the post-genome era, great progress has been made in metabolic engineering using recombinant DNA technology to enhance the production of high-value products by Streptomyces. With the development of microbial genome sequencing techniques and bioinformatic tools, a growing number of secondary metabolite (SM) biosynthetic gene clusters in Streptomyces and their biosynthetic logics have been uncovered and elucidated. In order to increase our knowledge about transcriptional regulators in SM of Streptomyces, this review firstly makes a comprehensive summary of the characterized factors involved in enhancing SM production and awakening SM biosynthesis...