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Sheo B. Singh - One of the best experts on this subject based on the ideXlab platform.
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antidiabetic and antisteatotic effects of the selective fatty acid synthase fas inhibitor Platensimycin in mouse models of diabetes
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Sheo B. Singh, Jun Wang, Christine C Chung, Gino Salituro, Bindhu V Karanam, Sang Ho Lee, Maryann Powles, Kenneth P Ellsworth, Michael E Lassman, Corey N MillerAbstract:Platensimycin (PTM) is a recently discovered broad-spectrum antibiotic produced by Streptomyces platensis. It acts by selectively inhibiting the elongation-condensing enzyme FabF of the fatty acid biosynthesis pathway in bacteria. We report here that PTM is also a potent and highly selective inhibitor of mammalian fatty acid synthase. In contrast to two agents, C75 and cerulenin, that are widely used as inhibitors of mammalian fatty acid synthase, Platensimycin specifically inhibits fatty acid synthesis but not sterol synthesis in rat primary hepatocytes. PTM preferentially concentrates in liver when administered orally to mice and potently inhibits hepatic de novo lipogenesis, reduces fatty acid oxidation, and increases glucose oxidation. Chronic administration of Platensimycin led to a net reduction in liver triglyceride levels and improved insulin sensitivity in db/+ mice fed a high-fructose diet. PTM also reduced ambient glucose levels in db/db mice. These results provide pharmacological proof of concept of inhibiting fatty acid synthase for the treatment of diabetes and related metabolic disorders in animal models.
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Platensimycin and platencin congeners from streptomyces platensis
Journal of Natural Products, 2011Co-Authors: Chaowei Zhang, Bruce Burgess, Hiranthi Jayasuriya, John G Ondeyka, Deborah L. Zink, Jun Wang, Lisa Dietrich, Ziqiang Guan, Kithsiri Herath, Sheo B. SinghAbstract:Platensimycin (1a) and platencin (2) are inhibitors of FabF and FabF/H bacterial fatty acid synthase. The discovery of natural congeners is an approach that can render a better understanding of the structure-function relationships of complex natural products. The isolation and structure elucidation of nine new congeners (11-20) of Platensimycin and platencin are described from a fermentation broth of Streptomyces platensis. These hydroxylated congeners are likely derived by cytochrome P450 oxidation of the terpenoid units post-cyclization. Polar groups in the terpenoid portion of the molecule produce negative interactions with the hydrophobic pocket of FabF, resulting in poor activities. However, the discovery of these compounds serves an important purpose, not only to understand structure-function relationships, which cannot be easily accessed by chemical modification, but also to provide access to compounds that could be used for structural identification/confirmation of the oxidative trace metabolites produced in vivo during animal experiments.
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Isolation, structure and biological activities of Platensimycin B_4 from Streptomyces platensis
The Journal of Antibiotics, 2009Co-Authors: Chaowei Zhang, Bruce Burgess, John G Ondeyka, Jun Wang, Lisa Dietrich, Ziqiang Guan, Sheo B. SinghAbstract:Platensimycin and platencin are inhibitors of FabF and FabF/H bacterial fatty acid synthesis enzymes, respectively. Discovery of natural congeners provides one of the ways to understand the relationship of chemical structure and biological function. Efforts to discover the natural analogs of Platensimycin by chemical screening led to the isolation of Platensimycin B_4, a glucoside congener of Platensimycin. This analog showed significantly attenuated activity and critically defined the limited binding space around the aromatic ring and established the importance of the free phenolic and carboxyl group for the activity.
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Isolation, structure and biological activities of Platensimycin B4 from Streptomyces platensis.
The Journal of antibiotics, 2009Co-Authors: Chaowei Zhang, Bruce Burgess, John G Ondeyka, Jun Wang, Lisa Dietrich, Ziqiang Guan, Sheo B. SinghAbstract:Isolation, structure and biological activities of Platensimycin B 4 from Streptomyces platensis
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Synthesis and biological evaluation of Platensimycin analogs.
Bioorganic & medicinal chemistry letters, 2009Co-Authors: Hong C. Shen, Sheo B. Singh, Jun Wang, Stephen M. Soisson, Srinivas Kodali, Gopalakrishnan Parthasarathy, Fa-xiang Ding, Xun Chen, Karen DorsoAbstract:Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of Platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity.
Kyriacos C. Nicolaou - One of the best experts on this subject based on the ideXlab platform.
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Proteomic signature of fatty acid biosynthesis inhibition available for in vivo mechanism of action studies
Antimicrobial agents and chemotherapy, 2011Co-Authors: Michaela Wenzel, Kyriacos C. Nicolaou, Nils Metzler-nolte, Malay Patra, Dirk Albrecht, David Y.‐k. Chen, Julia E. BandowAbstract:Fatty acid biosynthesis is a promising novel antibiotic target. Two inhibitors of fatty acid biosynthesis, platencin and Platensimycin, were recently discovered and their molecular targets identified. Numerous structure-activity relationship studies for both platencin and Platensimycin are currently being undertaken. We established a proteomic signature for fatty acid biosynthesis inhibition in Bacillus subtilis using platencin, Platensimycin, cerulenin, and triclosan. The induced proteins, FabHA, FabHB, FabF, FabI, PlsX, and PanB, are enzymes involved in fatty acid biosynthesis and thus linked directly to the target pathway. The proteomic signature can now be used to assess the in vivo mechanisms of action of compounds derived from structure-activity relationship programs, as demonstrated for the Platensimycin-inspired chromium bioorganometallic PM47. It will further serve as a reference signature for structurally novel natural and synthetic antimicrobial compounds with unknown mechanisms of action. In summary, we described a proteomic signature in B. subtilis consisting of six upregulated proteins that is diagnostic of fatty acid biosynthesis inhibition and thus can be applied to advance antibacterial drug discovery programs.
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Total Synthesis of Platensimycin and Related Natural Products
Journal of the American Chemical Society, 2009Co-Authors: Kyriacos C. Nicolaou, David J. Edmonds, G. Scott Tria, Shelby P. ElleryAbstract:Platensimycin is the flagship member of a new and growing class of antibiotics with promising antibacterial properties against drug-resistant bacteria. The total syntheses of Platensimycin and its congeners, Platensimycins B1 and B3, platensic acid, methyl platensinoate, platensimide A, homoplatensimide A, and homoplatensimide A methyl ester, are described. The convergent strategy developed toward these target molecules involved construction of their cage-like core followed by attachment of the various side chains through amide bond formation. In addition to a racemic synthesis, two asymmetric routes to the core structure are described: one exploiting a rhodium-catalyzed asymmetric cycloisomerization, and another employing a hypervalent iodine-mediated de-aromatizing cyclization of an enantiopure substrate. The final two bonds of the core structure were forged through a samarium diiodide-mediated ketyl radical cyclization and an acid-catalyzed etherification. The rhodium-catalyzed asymmetric reaction invo...
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Total Syntheses of (±)-Platencin and (−)-Platencin
Journal of the American Chemical Society, 2009Co-Authors: Kyriacos C. Nicolaou, David J. Edmonds, G. Scott Tria, Moumita KarAbstract:The secondary metabolites Platensimycin and platencin, isolated from the bacterial strain Streptomyces platensis, represent a novel class of natural products exhibiting unique and potent antibacterial activity. Platencin, though structurally similar to Platensimycin, has been found to operate through a slightly different mechanism of action involving the dual inhibition of lipid elongation enzymes FabF and FabH. Both natural products exhibit strong, broad-spectrum, Gram-positive antibacterial activity to key antibiotic resistant strains, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant Enterococcus faecium. Described herein are our synthetic efforts toward platencin, culminating in both racemic and asymmetric preparation of the natural product. The syntheses demonstrate the power of the cobalt-catalyzed asymmetric Diels−Alder reaction and the one-pot reductive rearrangement of [3.2.1] bicyclic ketones to [2.2.2] bicyclic olefins.
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Design, synthesis, and biological evaluation of Platensimycin analogues with varying degrees of molecular complexity
Journal of the American Chemical Society, 2008Co-Authors: Kyriacos C. Nicolaou, G. Scott Tria, Antonia Friederike Stepan, Troy Lister, Ana Montero, Craig I. Turner, Yefeng Tang, Jianhua Wang, Ross M. DentonAbstract:The molecular design, chemical synthesis, and biological evaluation of two distinct series of Platensimycin analogues with varying degrees of complexity are described. The first series of compounds probes the biological importance of the benzoic acid subunit of the molecule, while the second series explores the tetracyclic cage domain. The biological data obtained reveal that, while the substituted benzoic acid domain of Platensimycin is a highly conserved structural motif within the active compounds with strict functional group requirements, the cage domain of the molecule can tolerate considerable structural modifications without losing biological action. These findings refine our present understanding of the Platensimycin pharmacophore and establish certain structure-activity relationships from which the next generation of designed analogues of this new antibiotic may emerge.
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Total synthesis of complex heterocyclic natural products
Pure and Applied Chemistry, 2008Co-Authors: Kyriacos C. Nicolaou, Jason S. ChenAbstract:Total synthesis campaigns toward complex heterocyclic natural products are a prime source of inspiration for the design and execution of complex cascade sequences, powerful reactions, and efficient synthetic strategies. We highlight selected examples of such innovations in the course of our total syntheses of diazonamide A, azaspiracid-1, thio- strepton, 2,2'-epi-cytoskyrin A and rugulosin, abyssomicin C, Platensimycin, and unci- alamycin.
Yong Huang - One of the best experts on this subject based on the ideXlab platform.
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Stereoselective functionalization of Platensimycin and platencin by sulfa-Michael/aldol reactions.
Organic & biomolecular chemistry, 2019Co-Authors: Lin Qiu, Ben Shen, Zhongqing Wen, Kai Tian, Youchao Deng, Yanwen Duan, Yong HuangAbstract:Bioinspired sulfa-Michael/aldol cascade reactions have been developed for the semisynthesis of sulfur-containing heterocyclic derivatives of Platensimycin and platencin, with three newly formed contiguous stereogenic centers. Density functional theory calculations revealed the mechanism for the stereochemistry control. This method was used in a synthesis of a Platensimycin thiophene analogue with potent antibacterial activities against Staphylococcus aureus.
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stereoselective functionalization of Platensimycin and platencin by sulfa michael aldol reactions
Organic and Biomolecular Chemistry, 2019Co-Authors: Lin Qiu, Ben Shen, Zhongqing Wen, Kai Tian, Youchao Deng, Yanwen Duan, Yong HuangAbstract:Bioinspired sulfa-Michael/aldol cascade reactions have been developed for the semisynthesis of sulfur-containing heterocyclic derivatives of Platensimycin and platencin, with three newly formed contiguous stereogenic centers. Density functional theory calculations revealed the mechanism for the stereochemistry control. This method was used in a synthesis of a Platensimycin thiophene analogue with potent antibacterial activities against Staphylococcus aureus.
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Semisynthesis and Biological Evaluation of Platensimycin Analogues with Varying Aminobenzoic Acids.
ChemistrySelect, 2018Co-Authors: Kai Tian, Ben Shen, Youchao Deng, Yanwen Duan, Yong HuangAbstract:: Platensimycin (PTM) is an excellent natural product drug lead against various gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. In this study, twenty PTM derivatives with varying aminobenzoic acids were semisynthesized. In contrast to all the previous reported inactive aminobenzaote analogues, a few of them showed moderate antibacterial activities against S. aureus. Our study suggested that modification of the conserved aminobenzoic acid remains a viable approach to diversify the PTM scaffold.
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The semi-synthesis, biological evaluation and docking analysis of the oxime, hydrazine and hydrazide derivatives of Platensimycin
MedChemComm, 2018Co-Authors: Youchao Deng, Ben Shen, Yanwen Duan, Dingding Kang, Jie Shi, Wenqing Zhou, Aijun Sun, Xiangcheng Zhu, Yong HuangAbstract:A dozen oxime, hydrazine and hydrazide derivatives of Platensimycin (PTM) analogues were synthesized, some of which showed strong antibacterial activities and were shown to be stable under the bioassay conditions. Docking analysis revealed that they have certain new interactions with β-ketoacyl-[acyl carrier protein] synthase II (FabF), suggesting that Schiff base formation on its terpene scaffold is an effective strategy to diversify PTM structure.
Nils Metzler-nolte - One of the best experts on this subject based on the ideXlab platform.
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Sandwich and Half-Sandwich Derivatives of Platensimycin: Synthesis and Biological Evaluation
Organometallics, 2012Co-Authors: Malay Patra, Michaela Wenzel, Julia E. Bandow, Gilles Gasser, Klaus Merz, Nils Metzler-nolteAbstract:The multistep synthesis and biological evaluation of five structurally diverse, chiral and achiral CpMn(CO)3 (4, 7 and 8), (η6-arene)Cr(CO)3 (5), and [3]ferrocenophane-1-one (6) containing Platensimycin (1) derivatives are described in this report. The structures were inspired by the antibiotic Platensimycin. All the chiral compounds presented in this report are racemates. The new compounds were unambiguously characterized by 1H and 13C NMR spectroscopy, mass spectrometry, IR spectroscopy, and elemental analysis and in certain cases by X-ray crystallography (4, 16, 18, and 29). The antibacterial and antitumor activity of selected derivatives was tested. Molecular modeling suggests that the derivatives described here may well fit into the active site of the FabF enzyme, which is the biological target of Platensimycin. Hence, the antimicrobial activities of our new bioorganometallices 4–8 and the protected amide intermediates 15, 17, 18, 23, 28, 29, and 31 were tested against various Gram-positive and Gram-...
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Sandwich and Half-Sandwich Derivatives of Platensimycin: Synthesis and Biological Evaluation
2012Co-Authors: Malay Patra, Michaela Wenzel, Julia E. Bandow, Gilles Gasser, Klaus Merz, Nils Metzler-nolteAbstract:The multistep synthesis and biological evaluation of five structurally diverse, chiral and achiral CpMn(CO)3 (4, 7 and 8), (η6-arene)Cr(CO)3 (5), and [3]ferrocenophane-1-one (6) containing Platensimycin (1) derivatives are described in this report. The structures were inspired by the antibiotic Platensimycin. All the chiral compounds presented in this report are racemates. The new compounds were unambiguously characterized by 1H and 13C NMR spectroscopy, mass spectrometry, IR spectroscopy, and elemental analysis and in certain cases by X-ray crystallography (4, 16, 18, and 29). The antibacterial and antitumor activity of selected derivatives was tested. Molecular modeling suggests that the derivatives described here may well fit into the active site of the FabF enzyme, which is the biological target of Platensimycin. Hence, the antimicrobial activities of our new bioorganometallices 4–8 and the protected amide intermediates 15, 17, 18, 23, 28, 29, and 31 were tested against various Gram-positive and Gram-negative bacterial strains. However, all compounds were inactive up to concentrations of 180 μg/mL. The cytotoxicity of compounds 4 and 6 and the protected amide intermediates 15, 17, 18, 23, 28, 29, and 31 was tested against HepG2 and PT45 mammalian cancer cell lines. Surprisingly, all compounds containing a trimethylsilylethyl ester functionality at the aromatic ring (17, 23, 29, and 31) displayed rather high cytotoxicity between 2 and 9 μM
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Synthesis of Optically Active Ferrocene‐Containing Platensimycin Derivatives with a C6–C7 Substitution Pattern
European Journal of Inorganic Chemistry, 2011Co-Authors: Malay Patra, Michaela Wenzel, Julia E. Bandow, Gilles Gasser, Klaus Merz, Nils Metzler-nolteAbstract:Concurrently with the emergence of purely organic derivatives of the naturally occurring antibiotic Platensimycin (1a), herein, we describe the design, synthesis and biological evaluation of both the enantiomers of a C6–C7 ferrocene-fused Platensimycin derivative 2b. (S,SP)- and (R,RP)-2b were prepared in nine steps starting from commercially available 4-ferrocenyl-4-oxobutyric acid via highly diastereoselective Michael additions of optically active planar-chiral ferrocene-fused cyclohexanone derivatives (5) with acrylate ester as the key step. Manual superimposition of (S,SP)-2b on Platensimycin bound to the active site of its target enzyme FabF suggests that the former fits nicely in the active site and the C6–C7-fused ferrocene occupies a pocket similarly to the C8–C9-fused tetracyclic cage of 1a. Antimicrobial activities of (S,SP)- and (R,RP)-2b were tested against various Gram-positive and Gram-negative bacterial strains.
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Proteomic signature of fatty acid biosynthesis inhibition available for in vivo mechanism of action studies
Antimicrobial agents and chemotherapy, 2011Co-Authors: Michaela Wenzel, Kyriacos C. Nicolaou, Nils Metzler-nolte, Malay Patra, Dirk Albrecht, David Y.‐k. Chen, Julia E. BandowAbstract:Fatty acid biosynthesis is a promising novel antibiotic target. Two inhibitors of fatty acid biosynthesis, platencin and Platensimycin, were recently discovered and their molecular targets identified. Numerous structure-activity relationship studies for both platencin and Platensimycin are currently being undertaken. We established a proteomic signature for fatty acid biosynthesis inhibition in Bacillus subtilis using platencin, Platensimycin, cerulenin, and triclosan. The induced proteins, FabHA, FabHB, FabF, FabI, PlsX, and PanB, are enzymes involved in fatty acid biosynthesis and thus linked directly to the target pathway. The proteomic signature can now be used to assess the in vivo mechanisms of action of compounds derived from structure-activity relationship programs, as demonstrated for the Platensimycin-inspired chromium bioorganometallic PM47. It will further serve as a reference signature for structurally novel natural and synthetic antimicrobial compounds with unknown mechanisms of action. In summary, we described a proteomic signature in B. subtilis consisting of six upregulated proteins that is diagnostic of fatty acid biosynthesis inhibition and thus can be applied to advance antibacterial drug discovery programs.
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Proteomic Signature of Fatty Acid Biosynthesis Inhibition Available for In Vivo Mechanism-of-Action Studies
2011Co-Authors: Nils Metzler-nolte, Julia E. BAbstract:Fatty acid biosynthesis is a promising novel antibiotic target. Two inhibitors of fatty acid biosynthesis, platencin and Platensimycin, were recently discovered and their molecular targets identified. Numerous structure-activity relationship studies for both platencin and Platensimycin are currently being undertaken. We established a proteomic signature for fatty acid biosynthesis inhibition in Bacillus subtilis using platencin, Platensimycin, cerulenin, and triclosan. The induced proteins, FabHA, FabHB, FabF, FabI, PlsX, and PanB, are enzymes involved in fatty acid biosynthesis and thus linked directly to the target pathway. The proteomic signature can now be used to assess the in vivo mechanisms of action of compounds derived from structure-activity relationship programs, as demonstrated for the Platensimycin-inspired chromium bioorganometallic PM47. It will further serve as a reference signature for structurally novel natural and synthetic antimicrobial compounds with unknown mechanisms of action. In summary, we described a proteomic signature in B. subtili
Jun Wang - One of the best experts on this subject based on the ideXlab platform.
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antidiabetic and antisteatotic effects of the selective fatty acid synthase fas inhibitor Platensimycin in mouse models of diabetes
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Sheo B. Singh, Jun Wang, Christine C Chung, Gino Salituro, Bindhu V Karanam, Sang Ho Lee, Maryann Powles, Kenneth P Ellsworth, Michael E Lassman, Corey N MillerAbstract:Platensimycin (PTM) is a recently discovered broad-spectrum antibiotic produced by Streptomyces platensis. It acts by selectively inhibiting the elongation-condensing enzyme FabF of the fatty acid biosynthesis pathway in bacteria. We report here that PTM is also a potent and highly selective inhibitor of mammalian fatty acid synthase. In contrast to two agents, C75 and cerulenin, that are widely used as inhibitors of mammalian fatty acid synthase, Platensimycin specifically inhibits fatty acid synthesis but not sterol synthesis in rat primary hepatocytes. PTM preferentially concentrates in liver when administered orally to mice and potently inhibits hepatic de novo lipogenesis, reduces fatty acid oxidation, and increases glucose oxidation. Chronic administration of Platensimycin led to a net reduction in liver triglyceride levels and improved insulin sensitivity in db/+ mice fed a high-fructose diet. PTM also reduced ambient glucose levels in db/db mice. These results provide pharmacological proof of concept of inhibiting fatty acid synthase for the treatment of diabetes and related metabolic disorders in animal models.
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Platensimycin and Platencin Congeners from Streptomyces platensis
Journal of natural products, 2011Co-Authors: Chaowei Zhang, Bruce Burgess, Hiranthi Jayasuriya, John G Ondeyka, Deborah L. Zink, Lisa Dietrich, Ziqiang Guan, Kithsiri Herath, Jun WangAbstract:Platensimycin (1a) and platencin (2) are inhibitors of FabF and FabF/H bacterial fatty acid synthase. The discovery of natural congeners is an approach that can render a better understanding of the structure−function relationships of complex natural products. The isolation and structure elucidation of nine new congeners (11−20) of Platensimycin and platencin are described from a fermentation broth of Streptomyces platensis. These hydroxylated congeners are likely derived by cytochrome P450 oxidation of the terpenoid units post-cyclization. Polar groups in the terpenoid portion of the molecule produce negative interactions with the hydrophobic pocket of FabF, resulting in poor activities. However, the discovery of these compounds serves an important purpose, not only to understand structure−function relationships, which cannot be easily accessed by chemical modification, but also to provide access to compounds that could be used for structural identification/confirmation of the oxidative trace metabolites ...
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Platensimycin and platencin congeners from streptomyces platensis
Journal of Natural Products, 2011Co-Authors: Chaowei Zhang, Bruce Burgess, Hiranthi Jayasuriya, John G Ondeyka, Deborah L. Zink, Jun Wang, Lisa Dietrich, Ziqiang Guan, Kithsiri Herath, Sheo B. SinghAbstract:Platensimycin (1a) and platencin (2) are inhibitors of FabF and FabF/H bacterial fatty acid synthase. The discovery of natural congeners is an approach that can render a better understanding of the structure-function relationships of complex natural products. The isolation and structure elucidation of nine new congeners (11-20) of Platensimycin and platencin are described from a fermentation broth of Streptomyces platensis. These hydroxylated congeners are likely derived by cytochrome P450 oxidation of the terpenoid units post-cyclization. Polar groups in the terpenoid portion of the molecule produce negative interactions with the hydrophobic pocket of FabF, resulting in poor activities. However, the discovery of these compounds serves an important purpose, not only to understand structure-function relationships, which cannot be easily accessed by chemical modification, but also to provide access to compounds that could be used for structural identification/confirmation of the oxidative trace metabolites produced in vivo during animal experiments.
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Isolation, structure and biological activities of platencin A2–A4 from Streptomyces platensis
Bioorganic & medicinal chemistry, 2010Co-Authors: Chaowei Zhang, John G Ondeyka, Lisa Dietrich, Francis P. Gailliot, Michelle Hesse, Michael Lester, Karen Dorso, Mary Motyl, Jun WangAbstract:Natural products serve as a great reservoir for chemical diversity and are the greatest source for antibacterial agents. Recent discoveries of Platensimycin and platencin as inhibitors of bacterial fatty acid biosynthesis enzymes supplied new chemical scaffolds for potential antibacterial agents to overcome resistant pathogens. Discovery of natural congeners augment chemical modification in understanding of structure–activity relationship (SAR). Chemical and biological screening of the extracts led to isolation of three hydroxylated analogs of platencin. The C-12, C-14 and C-15 hydroxylated analogs showed attenuated activities which provided significant understanding of functional tolerance in the diterpenoid portion of the molecule. A truncated and oxidized C-13 natural congener was isolated which suggested direct intermediacy of ent-copalyl diphosphate for the biosynthesis of Platensimycins and platencins.
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Isolation, structure and biological activities of Platensimycin B_4 from Streptomyces platensis
The Journal of Antibiotics, 2009Co-Authors: Chaowei Zhang, Bruce Burgess, John G Ondeyka, Jun Wang, Lisa Dietrich, Ziqiang Guan, Sheo B. SinghAbstract:Platensimycin and platencin are inhibitors of FabF and FabF/H bacterial fatty acid synthesis enzymes, respectively. Discovery of natural congeners provides one of the ways to understand the relationship of chemical structure and biological function. Efforts to discover the natural analogs of Platensimycin by chemical screening led to the isolation of Platensimycin B_4, a glucoside congener of Platensimycin. This analog showed significantly attenuated activity and critically defined the limited binding space around the aromatic ring and established the importance of the free phenolic and carboxyl group for the activity.