01775nas a2200241   4500008004100000245010900041210006900150260000800219300001600227490000600243520093200249100002701181700002201208700001901230700002601249700002501275700001701300700002601317700002001343700003201363700001601395856012201411       2017                        eng d00aAnti-microbial activity of chrysomycin a produced by streptomyces sp. against mycobacterium tuberculosis0 aAntimicrobial activity of chrysomycin a produced by streptomyces  cJUL  a36335-363390 v73 aLimited efficacy of the BCG (Bacillus Calmette–Guérin) vaccine against adult tuberculosis and the emergence of resistance to existing anti-tuberculosis drugs compel discovery of novel antibiotics against Mycobacterium tuberculosis. Actinomycetes are still an attractive platform for the discovery of new antimicrobials, especially from untapped natural hotspots, despite the belief that they are an exhausted resource after repeated re-discoveries. Herein we report the isolation and identification of chrysomycin A from an actinomycete isolated from a coastal area in Kerala. We show for the first time that it has antimycobacterial activity. It was found to be bactericidal to planktonic and intracellular M. tuberculosis with an MIC of 3.125 μg mL⁻¹; it is non-hemolytic and has negligible cytotoxicity. The actinomycete that produces chrysomycin A was found to be a Streptomyces sp. through 16S rRNA gene sequencing.1 aBalaji, Muralikrishnan1 aDan, Vipin, Mohan1 aJoseph, Vinodh1 aJamsheena, Vellekkatt1 aRamachandran, Ranjit1 aThomas, Sabu1 aDastager, Syed, Gulam1 aKumar, Santhosh1 aLankalapalli, Ravi, Shankar1 aKumar, Ajay  uhttps://library.ncl.res.in/content/anti-microbial-activity-chrysomycin-produced-streptomyces-sp-against-mycobacterium02406nas a2200289   4500008004100000022001400041245015700055210006900212260000800281300000900289490000600298520137000304100002201674700002701696700001901723700001901742700003101761700003601792700001801828700002001846700002301866700002101889700003401910700001601944700003301960856012301993       2018                        eng d  a2045-232200aStreptomyces sp metabolite(s) promotes Bax mediated intrinsic apoptosis and autophagy involving inhibition of mTOR pathway in cervical cancer cell lines0 aStreptomyces sp metabolites promotes Bax mediated intrinsic apop  cFEB  a28100 v83 a<p>In cervical cancer, the association between HPV infection and dysregulation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway (PI3K/AKT/mTOR pathway) places mTOR as an attractive therapeutic target. The failure of current treatment modalities in advanced stages of this cancer and drawbacks of already available mTOR inhibitors demand for novel drug candidates. In the present study we identified the presence of a mTOR inhibitor in an active fraction of the ethyl acetate extract of Streptomyces sp OA293. The metabolites(s) in the active fraction completely inhibited mTORC1 and thereby suppressed activation of both of its downstream targets, 4E-BP1 and P70S6k, in cervical cancer cells. In addition, it also stalled Akt activation via inhibition of mTORC2. The mechanism of mTOR inhibition detailed in our study overcomes significant drawbacks of well known mTOR inhibitors such as rapamycin and rapalogs. The active fraction induced autophagy and Bax mediated apoptosis suggesting that mTOR inhibition resulted in programmed cell death of cancer cells. The molecular weight determination of the components in active fraction confirmed the absence of any previously known natural mTOR inhibitor. This is the first report of complete mTOR complex inhibition by a product derived from microbial source.</p>1 aDan, Vipin, Mohan1 aMuralikrishnan, Balaji1 aSanawar, Rahul1 aVinodh, J., S.1 aBurkul, Bhushan, Bapusaheb1 aSrinivas, Kalanghad, Puthankala1 aLekshmi, Asha1 aPradeep, N., S.1 aDastager, Syed, G.1 aSanthakumari, B.1 aSanthoshkumar, Thankayyan, R.1 aKumar, Ajay1 aPillai, Madhavan, Radhakrish  uhttps://library.ncl.res.in/content/streptomyces-sp-metabolites-promotes-bax-mediated-intrinsic-apoptosis-and-autophagy02408nas a2200253   4500008004100000022001400041245014400055210006900199260000800268300001200276490000700288520152200295100002201817700001901839700002001858700001901878700001801897700001601915700002601931700002501957700002301982700002502005856012402030       2020                        eng d  a1554-892900aMolecular networking and whole-genome analysis aid discovery of an angucycline that inactivates mTORC1/C2 and induces programmed cell death0 aMolecular networking and wholegenome analysis aid discovery of a  cMAR  a780-7880 v153 a<p>Rediscovery of known compounds and time consumed in identification, especially high molecular weight compounds with complex structure, have let down interest in drug discovery. In this study, whole-genome analysis of microbe and Global Natural Products Social (GNPS) molecular networking helped in initial understanding of possible compounds produced by the microbe. Genome data revealed 10 biosythethic gene clusters that encode for secondary metabolites with anticancer potential. NMR analysis of the pure compound revealed the presence of a four-ringed benz[a]anthracene, thus confirming angucycline; molecular networking further confirmed production of this class of compounds. The type II polyketide synthase gene identified in the microbial genome was matched with the urdamycin duster by BLAST analysis. This information led to ease in identification of urdamycin E and a novel natural derivative, urdamycin V, purified from Streptomyces sp. OA293. Urdamycin E (Urd E) induced apoptosis and autophagy in cancer cell lines. Urd E exerted anticancer action through inactivation of the mTOR complex by preventing phosphorylation at Ser 2448 and Ser 2481 of mTORC1 and mTORC2, respectively. Significant reduction in phosphorylation of the major downstream regulators of both mTORC1 (p70s6k and 4e-bp1) and mTORC2 (Akt) were observed, thus further confirming complete inhibition of the mTOR pathway. Urd E presents itself as a novel mTOR inhibitor that employs a novel mechanism in mTOR pathway inhibition.</p>
1 aDan, Vipin, Mohan1 aVinodh, J., S.1 aSandesh, C., J.1 aSanawar, Rahul1 aLekshmi, Asha1 aKumar, Ajay1 aKumar, T., R. Santhos1 aMarelli, Uday, Kiran1 aDastager, Syed, G.1 aPillai, Radhakrishna  uhttps://library.ncl.res.in/content/molecular-networking-and-whole-genome-analysis-aid-discovery-angucycline-inactivates