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Fotso S.,University of Oregon | Santosa D.A.,Indonesian Center for Biodiversity and Biotechnology | Santosa D.A.,Bogor Agricultural University | Saraswati R.,Bogor Agricultural University | And 4 more authors.
Journal of Natural Products | Year: 2010

Fractionation of the extract from the Indonesian Streptomyces sp. ICBB8198 as directed by the antibacterial activity delivered the known phenazine antibiotics griseoluteic acid (1a) and griseolutein A (1b), as well as two new phenazine derivatives (2 and 3). In addition, the known compounds spirodionic acid, dihydrosarkomycins, and 6-ethyl-4-hydroxy-3,5-dimethyl-2H-pyran-2-one (4a), along with the new pyrone 3,6-diethyl-4-hydroxy-5-methyl-2H-pyran-2-one (4b), were isolated. We report here the isolation, structure elucidation, and antibiotic activity of the new metabolites as well as a hypothetical pathway for the formation of the new phenazine derivatives. © 2010 American Chemical Society and American Society of Pharmacognosy.


Sheng Y.,Oregon State University | Fotso S.,Oregon State University | Fotso S.,Dow AgroSciences | Serrill J.D.,Oregon State University | And 7 more authors.
Organic Letters | Year: 2015

Two new apoptolidins, 2′-O-succinyl-apoptolidin A (11) and 3′-O-succinyl-apoptolidin A (12), were isolated from the culture broth of an Indonesian Amycolatopsis sp. ICBB 8242. These compounds inhibit the proliferation and viability of human H292 and HeLa cells. However, in contrast to apoptolidin A (1), they do not inhibit cellular respiration in H292 cells. It is proposed that apoptolidins are produced and secreted in their succinylated forms and 1 is the hydrolysis product of 11 and 12. (Figure Presented). © 2015 American Chemical Society.


Serrill J.D.,Oregon State University | Tan M.,Oregon State University | Fotso S.,Oregon State University | Fotso S.,Dow AgroSciences | And 14 more authors.
Biochemical Pharmacology | Year: 2015

Apoptolidin A was first isolated as a secondary metabolite of a Nocardiopsis sp. and is the founding member of a family of potential selective cancer cell toxins. We now report the isolation, production and pharmacological characterization of apoptolidins A and C from an alternate actinomycete producer, an Amycolatopsis sp. from soil samples collected in Indonesia. We investigated the action of apoptolidins A and C in representative human glioblastoma cells, lung cancer cells and mouse embryonic fibroblasts (MEFs) to better understand the mechanism of action of the known apoptolidins. Shifts in cellular metabolism in intact cells and the status of the AMP-activated protein kinase (AMPK) stress pathway in response to apoptolidin A were entirely consistent with the actions of an ATP synthase inhibitor. We find the metabolic phenotype of the cell to be a critical determinant of apoptolidin sensitivity and the likely basis for cancer cell selectivity. The apoptolidins induce indirect activation of AMPK and trigger autophagy in sensitive cell types without significant inhibition of mTORC1. Human U87-MG glioblastoma cells and wild type MEFs showed increased phosphorylation of AMPK (Thr172), ACC (Ser79) and ULK1 (Ser555), whereas AMPKα-null MEFs and more glycolytic SF-295 glioblastoma cells lacked this response. Although both are reported to be selective inhibitors of mitochondrial ATP synthase, differences between apoptolidin- and oligomycin A-induced responses in cells indicate that the action of these macrolides is not identical. © 2014 Elsevier Inc. All rights reserved.


Serrill J.D.,Oregon State University | Tan M.,Oregon State University | Fotso S.,Oregon State University | Sikorska J.,Oregon State University | And 12 more authors.
Biochemical Pharmacology | Year: 2014

Apoptolidin A was first isolated as a secondary metabolite of a Nocardiopsis sp. and is the founding member of a family of potential selective cancer cell toxins. We now report the isolation, production and pharmacological characterization of apoptolidins A and C from an alternate actinomycete producer, an Amycolatopsis sp. from soil samples collected in Indonesia. We investigated the action of apoptolidins A and C in representative human glioblastoma cells, lung cancer cells and mouse embryonic fibroblasts (MEFs) to better understand the mechanism of action of the known apoptolidins. Shifts in cellular metabolism in intact cells and the status of the AMP-activated protein kinase (AMPK) stress pathway in response to apoptolidin A were entirely consistent with the actions of an ATP synthase inhibitor. We find the metabolic phenotype of the cell to be a critical determinant of apoptolidin sensitivity and the likely basis for cancer cell selectivity. The apoptolidins induce indirect activation of AMPK and trigger autophagy in sensitive cell types without significant inhibition of mTORC1. Human U87-MG glioblastoma cells and wild type MEFs showed increased phosphorylation of AMPK (Thr172), ACC (Ser79) and ULK1 (Ser555), whereas AMPKα-null MEFs and more glycolytic SF-295 glioblastoma cells lacked this response. Although both are reported to be selective inhibitors of mitochondrial ATP synthase, differences between apoptolidin- and oligomycin A-induced responses in cells indicate that the action of these macrolides is not identical. © 2014 Elsevier Inc.


Santosa D.A.,Bogor Agricultural University | Sulastri,Indonesian Center for Biodiversity and Biotechnology | Sarjito,Bogor Agricultural University
Biotropia | Year: 2010

This study is aimed to get lipid producing microalgae as feedstock for biofuel production. The microalgae were isolated from 355 collected water samples which represented many distinct ecosystems such as paddy fields, rivers, agricultural dams, ponds, swampy areas and unique ecosystem of volcano and mud-volcano craters in West- and Central Java, Indonesia. A total of 267 strains of microalgae were isolated from the samples of which 221 strains of them have capability to produce lipid. There were four promising strains that produce lipid between 14.7 - 45.7 percent dry weight in optimal condition that were identified as Chlamydomonas sp. KO-7267 and PK-7l95, Cblorellasp. KS-7300 and Desmodesmussp. BK-729l.


Sheng Y.,Oregon State University | Lam P.W.,Oregon State University | Shahab S.,Indonesian Center for Biodiversity and Biotechnology | Santosa D.A.,Indonesian Center for Biodiversity and Biotechnology | And 4 more authors.
Journal of Natural Products | Year: 2015

Four new elaiophylin macrolides (1-4), together with five known elaiophylins (5-9), have been isolated from cultures of the Indonesian soil bacterium Streptomyces sp. ICBB 9297. The new compounds have macrocyclic skeletons distinct from those of the known dimeric elaiophylins in that one or both of the polyketide chains contain(s) an additional pendant methyl group. Further investigations revealed that 1 and 2 were derived from 3 and 4, respectively, during isolation processes. Compounds 1-3 showed comparable antibacterial activity to elaiophylin against Staphylococcus aureus. However, interestingly, only compounds 1 and 3, which contain a pendant methyl group at C-2, showed activity against Mycobacterium smegmatis, whereas compound 2, which has two pendant methyl groups at C-2 and C-2′, and the known elaiophylin analogues (5-7), which lack pendant methyl groups at C-2 and/or C-2′, showed no activity. The production of 3 and 4 in strain ICBB 9297 indicates that one of the acyltransferase (AT) domains in the elaiophylin polyketide synthases (PKSs) can recruit both malonyl-CoA and methylmalonyl-CoA as substrates. Bioinformatic analysis of the AT domains of the elaiophylin PKSs revealed that the ela-AT7 domain contains atypical active site amino acid residues, distinct from those conserved in malonyl-CoA- or methylmalonyl-CoA-specific ATs. © 2015 The American Chemical Society and American Society of Pharmacognosy.


PubMed | Indonesian Center for Biodiversity and Biotechnology and Oregon State University
Type: Journal Article | Journal: Journal of natural products | Year: 2015

Four new elaiophylin macrolides (1-4), together with five known elaiophylins (5-9), have been isolated from cultures of the Indonesian soil bacterium Streptomyces sp. ICBB 9297. The new compounds have macrocyclic skeletons distinct from those of the known dimeric elaiophylins in that one or both of the polyketide chains contain(s) an additional pendant methyl group. Further investigations revealed that 1 and 2 were derived from 3 and 4, respectively, during isolation processes. Compounds 1-3 showed comparable antibacterial activity to elaiophylin against Staphylococcus aureus. However, interestingly, only compounds 1 and 3, which contain a pendant methyl group at C-2, showed activity against Mycobacterium smegmatis, whereas compound 2, which has two pendant methyl groups at C-2 and C-2, and the known elaiophylin analogues (5-7), which lack pendant methyl groups at C-2 and/or C-2, showed no activity. The production of 3 and 4 in strain ICBB 9297 indicates that one of the acyltransferase (AT) domains in the elaiophylin polyketide synthases (PKSs) can recruit both malonyl-CoA and methylmalonyl-CoA as substrates. Bioinformatic analysis of the AT domains of the elaiophylin PKSs revealed that the ela_AT7 domain contains atypical active site amino acid residues, distinct from those conserved in malonyl-CoA- or methylmalonyl-CoA-specific ATs.

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