β-carboline biomediators induce reveromycin production in Streptomyces sp. SN-593

Panthee, Suresh; Takahashi, Shunji; Hayashi, Teruo; Shimizu, Takeshi; Osada, Hiroyuki

doi:10.1038/s41598-019-42268-w

Cited by 7 publications

(12 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, the equilibrium affinity constant of 1.31 μM calculated for BR-1 was almost identical to its bioactive concentration (Fig. S4B) 28 . Additionally, we have found that the tetrahydro form of BR-1 (3) ( Fig.…”

Section: Revu As the Molecular Target Of Br-1mentioning

confidence: 57%

“…Additionally, we have found that the tetrahydro form of BR-1 (3) ( Fig. 1) did not induce the production of RMs 28 . As expected, the sensorgram for 3 did not reach saturation at a concentration of up to 87 μM, indicative of non-specific binding (Fig.…”

Section: Revu As the Molecular Target Of Br-1mentioning

confidence: 79%

“…The EC 50 value was about half the concentration required for inducing RM production (0.35 µM) 28 . We have found that the tetrahydro form of BR-1 (3) did not induce the production of RMs 28 . Consistently, 3 did not enhance RevU binding to DNA (Fig.…”

Section: Revu As the Molecular Target Of Br-1mentioning

confidence: 93%

“…SN-593 ( Fig. 1) 28 . BR-1 enhanced RM production without affecting cell growth and was demonstrated as an external chemical trigger for increasing SM 28 .…”

mentioning

confidence: 99%

“…1) 28 . BR-1 enhanced RM production without affecting cell growth and was demonstrated as an external chemical trigger for increasing SM 28 . In this study, we define BR-1 as biomediator to distinguish them from autoregulators, which are produced intracellularly to regulate functions in the cells that produced them.…”

mentioning

confidence: 99%

See 4 more Smart Citations

β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593

Panthee

Kito

Hayashi

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Actinomycetes bacteria produce diverse bioactive molecules that are useful as drug seeds. to improve their yield, researchers often optimize the fermentation medium. However, exactly how the extracellular chemicals present in the medium activate secondary metabolite gene clusters remains unresolved. BR-1, a β-carboline compound, was recently identified as a chemical signal that enhanced reveromycin A production in Streptomyces sp. SN-593. Here we show that BR-1 specifically bound to the transcriptional regulator protein RevU in the reveromycin A biosynthetic gene cluster, and enhanced RevU binding to its promoter. RevU belongs to the LuxR family regulator that is widely found in bacteria. Interestingly, BR-1 and its derivatives also enhanced the production of secondary metabolites in other Streptomyces species. Although LuxR-N-acyl homoserine lactone systems have been characterized in Gram-negative bacteria, we revealed LuxR-β-carboline system in Streptomyces sp. SN-593 for the production of secondary metabolites. This study might aid in understanding hidden chemical communication by β-carbolines. Microorganisms utilize a variety of communication systems that enable them to send and receive chemical signals to one another 1. Quorum sensing is one cell-cell communication mechanism. Gram-negative bacteria produce hormone-like signals, such as the release of acyl-homoserine lactones, to control cellular responses 2,3. Streptomyces, a soil-dwelling gram-positive bacteria, utilize autoregulatory hormones to produce a variety of secondary metabolites (SMs) 4. The classical example of such hormone is A-factor in Streptomyces griseus 5 , and the structurally diverse autoregulators such as 2-alkyl-4-hydroxymethylfuran-3-carboxylic acids in Streptomyces coelicolor 6 , PI factor in Streptomyces natalensis 7 , avenolide in Streptomyces avermitilis 8 , VB-A in Streptomyces virginiae 9 , IM-2 in Streptomyces sp. FRI-5 10 , SCB1 in Streptomyces coelicolor 11 , and SRB1 in Streptomyces rochei 12 are also known to promote morphological development and regulating secondary metabolism. These have been extensively reviewed elsewhere 13-15. On the other hand, chemical signals derived from extra-species/environmental stimuli such as hormaomycin 16 , goadsporin 17 , promomycin 18 , antibiotic-remodeling compounds (ARCs) 19 , and rare earth elements 20 also induce morphogenesis and SM production in Streptomyces species at higher concentration range compared to autoregulators. Co-culturing Streptomyces with mycolic acid-containing bacteria was found to also induce SM production 21. Except for some ARCs, which inhibit fatty acid biosynthesis, the mechanisms of how extracellular chemical signals activate SM biosynthesis have not been clarified. Reveromycin (RM) A was identified from Streptomyces sp. SN-593 as an inhibitor of the mitogenic activity of epidermal growth factor 22. It also inhibits bone resorption specifically in osteoclast 23. The RM biosynthetic gene cluster consists of 21 genes, including three transcriptional regulators 24...

show abstract

Section: Revu As the Molecular Target Of Br-1mentioning

confidence: 57%

Section: Revu As the Molecular Target Of Br-1mentioning

confidence: 79%

Section: Revu As the Molecular Target Of Br-1mentioning

confidence: 93%

“…SN-593 ( Fig. 1) 28 . BR-1 enhanced RM production without affecting cell growth and was demonstrated as an external chemical trigger for increasing SM 28 .…”

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593

Panthee

Kito

Hayashi

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-94

et al. 2021

Self Cite

View full text Add to dashboard Cite

A recently discovered secondary metabolism regulator, NPD938, was used to alter the secondary metabolite profile in Fusarium sp. RK97-94. Three lucilactaene analogues were detected via UPLC-ESI-MS analysis in NPD938-treated culture. The three metabolites were successfully purified and identified as dihydroNG391 (1), dihydrolucilactaene (2), and 13α-hydroxylucilactaene (3) via extensive spectroscopic analyses. DihydroNG391 (1) exhibited weak in vitro antimalarial activity (IC 50 = 62 μM). In contrast, dihydrolucilactaene (2) and 13α-hydroxylucilactaene (3) showed very potent antimalarial activity (IC 50 = 0.0015 and 0.68 μM, respectively). These findings provide insight into the structure−activity relationship of lucilactaene and its analogues as antimalarial lead compounds.

show abstract

Expression of Syo_1.56 SARP Regulator Unveils Potent Elasnin Derivatives with Antibacterial Activity

A. Abdelhakim,

Futamura,

Asami

et al. 2024

J. Nat. Prod.

Self Cite

View full text Add to dashboard Cite

Actinomycetes are prolific producers of natural products, particularly antibiotics. However, a significant proportion of its biosynthetic gene clusters (BGCs) remain silent under typical laboratory conditions. This limits the effectiveness of conventional isolation methods for the discovery of novel natural products. Genetic interventions targeting the activation of silent gene clusters are necessary to address this challenge. Streptomyces antibiotic regulatory proteins (SARPs) act as cluster-specific activators and can be used to target silent BGCs for the discovery of new antibiotics. In this study, the expression of a previously uncharacterized SARP protein, Syo_1.56, in Streptomyces sp. RK18-A0406 significantly enhanced the production of known antimycins and led to the discovery of 12 elasnins (1−12), 10 of which were novel. The absolute stereochemistry of elasnin A 1 was assigned for the first time to be 6S. Unexpectedly, Syo_1.56 seems to function as a pleiotropic rather than cluster-specific SARP regulator, with the capability of co-regulating two distinct biosynthetic pathways, simultaneously. All isolated elasnins were active against wild-type and methicillin-resistant Staphylococcus aureus with IC 50 values of 0.5−20 μg/mL, some of which (elasnins A 1 , B 2 , and C 1 and proelasnins A 1 , and C 1 ) demonstrated moderate to strong antimalarial activities against Plasmodium falciparum 3D7. Elasnins A 1 , B 3 , and C 1 also showed in vitro inhibition of the metallo-β-lactamase responsible for the development of highly antibiotic-resistant bacterial strains.

show abstract

β-carboline biomediators induce reveromycin production in Streptomyces sp. SN-593

Cited by 7 publications

References 31 publications

β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593

β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593

Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-94

Expression of Syo_1.56 SARP Regulator Unveils Potent Elasnin Derivatives with Antibacterial Activity

Contact Info

Product

Resources

About