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platensimycin and platencin biosynthesis.

(2011) Dedicated ent-kaurene and ent-atiserene synthases for platensimycin and platencin biosynthesis.

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List of antibiotics - Wikipedia

Platensimycin, platencin, and phomallenic acids, newly discovered natural product inhibitors of the condensation steps in fatty acid biosynthesis, represent new classes of compounds with antibiotic potential.

T1 - Dedicated ent-kaurene and ent-atiserene synthases for platensimycin and platencin biosynthesis

AB - Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of bacterial and mammalian fatty acid synthases and have emerged as promising drug leads for both antibacterial and antidiabetic therapies. Comparative analysis of the PTM and PTN biosynthetic machineries in Streptomyces platensis MA7327 and MA7339 revealed that the divergence of PTM and PTN biosynthesis is controlled by dedicated ent-kaurene and ent-atiserene synthases, the latter of which represents a new pathway for diterpenoid biosynthesis. The PTM and PTN biosynthetic machineries provide a rare glimpse at how secondary metabolic pathway evolution increases natural product structural diversity and support the wisdom of applying combinatorial biosynthesis methods for the generation of novel PTM and/or PTN analogues, thereby facilitating drug development efforts based on these privileged natural product scaffolds.

The following is a list of antibiotics

Two inhibitors of fatty acid biosynthesis, platencin and platensimycin, were recently discovered and their molecular targets identified.

Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of bacterial and mammalian fatty acid synthases and have emerged as promising drug leads for both antibacterial and antidiabetic therapies. Comparative analysis of the PTM and PTN biosynthetic machineries in Streptomyces platensis MA7327 and MA7339 revealed that the divergence of PTM and PTN biosynthesis is controlled by dedicated ent-kaurene and ent-atiserene synthases, the latter of which represents a new pathway for diterpenoid biosynthesis. The PTM and PTN biosynthetic machineries provide a rare glimpse at how secondary metabolic pathway evolution increases natural product structural diversity and support the wisdom of applying combinatorial biosynthesis methods for the generation of novel PTM and/or PTN analogues, thereby facilitating drug development efforts based on these privileged natural product scaffolds.

N2 - Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of bacterial and mammalian fatty acid synthases and have emerged as promising drug leads for both antibacterial and antidiabetic therapies. Comparative analysis of the PTM and PTN biosynthetic machineries in Streptomyces platensis MA7327 and MA7339 revealed that the divergence of PTM and PTN biosynthesis is controlled by dedicated ent-kaurene and ent-atiserene synthases, the latter of which represents a new pathway for diterpenoid biosynthesis. The PTM and PTN biosynthetic machineries provide a rare glimpse at how secondary metabolic pathway evolution increases natural product structural diversity and support the wisdom of applying combinatorial biosynthesis methods for the generation of novel PTM and/or PTN analogues, thereby facilitating drug development efforts based on these privileged natural product scaffolds.

PTM; Platensimycin (PTM) is an antibiotic produced by S

We established a proteomic signature for fatty acid biosynthesis inhibition in Bacillus subtilis using platencin, platensimycin, cerulenin, and triclosan.

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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  • Platensimycin ≥90% (HPLC), from Streptomyces …

    Dedicated ent-kaurene and ent-atiserene synthases for platensimycin and platencin biosynthesis.

  • Proteomic Signature of Fatty Acid Biosynthesis …

    Shen and co-workers deduced the details of platensimycin’s biosynthesis by analyzing its biosynthetic gene clusters.

  • 19/01/2011 · ABSTRACT

    The highest division is between bactericidal antibiotics and bacteriostatic antibiotics

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Fatty acid biosynthesis is a promising novel antibiotic target

Singh on a study whose findings have been published in the Journal of the American Chemical Society, in a paper titled "Biosynthetic Studies of Platensimycin" (Herath, K.

Platensimycin story | Chemical & Engineering News

Since the recent discovery of platencin and platensimycin, two potent natural inhibitors of bacterial growth from Streptomyces platensis (, , , ), there is renewed interest in fatty acid biosynthesis as an antibacterial target. Platensimycin as well as cerulenin, discovered in the 1960s, inhibit the 3-oxoacyl-acyl carrier protein (ACP) synthase II FabF (, ), whereas platencin inhibits both FabF and 3-oxoacyl-ACP synthases III FabHA and FabHB (, ). These enzymes catalyze the initial condensation of acyl-ACPs and existing fatty acid chains with malonyl-ACP, respectively (). In contrast, triclosan, another fatty acid biosynthesis inhibitor, discovered in the 1970s, targets the second reduction step in the fatty acid chain elongating biosynthesis cycle, inhibiting the enoyl-ACP reductase FabI () (see for an overview). Neither triclosan nor cerulenin is used clinically as an antimicrobial agent. However, triclosan is used in consumer products, such as toothpaste (, , ), while cerulenin is currently being evaluated as an antitumor therapeutic in combination therapies (). Platensimycin and platencin showed efficacy in a Staphylococcus aureus mouse infection model (). A number of structure-activity relationship (SAR) studies are being performed to identify lead structures for further development (, , , ). In addition, the search for effective natural analogues continues (, , ).

inhibits fatty acid biosynthesis by blocking an enoyl-ACP reductase.

In this study we investigated the bacterial response to fatty acid biosynthesis inhibitors triclosan, cerulenin, platensimycin, and platencin. On the basis of the proteomic response profiles of B. subtilis, we were able to establish a proteomic signature for fatty acid biosynthesis inhibition. We then applied the newly established signature to investigate the mechanism of action of the chromium bioorganometallic PM47, a compound inspired by platensimycin, which displayed low activity against Gram-positive bacteria (). On the basis of the findings of proteome analysis, we could rule out fatty acid biosynthesis as its primary mechanism of action.

A Review on Platensimycin: A Selective FabF Inhibitor

To establish an antibiotic proteomic signature for fatty acid biosynthesis inhibition, the protein synthesis patterns of triclosan, cerulenin, platensimycin, and platencin were compared to identify common responder proteins. Reproducibility of the proteome response patterns for each of the antibiotics is absolutely critical and highly dependent on reproducibility of the cellular growth and antibiotic treatment conditions. Differences in antibiotic concentration, cell density, or incubation time may have a significant impact on protein synthesis profiles. This is of particular concern, when an antibiotic mode of action is known to shift in a concentration-dependent manner. Triclosan, e.g., inhibits fatty acid biosynthesis at low concentrations but at higher doses also damages multiple cytoplasmic and membrane targets (, , ).

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