https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

▪ Abstract The type II fatty acid synthetic pathway is the principal route for the production of membrane phospholipid acyl chains in bacteria and plants. The reaction sequence is carried out by a series of individual soluble proteins that are each encoded by a discrete gene, and the pathway intermediates are shuttled between the enzymes as thioesters of an acyl carrier protein. The Escherichia coli system is the paradigm for the study of this system, and high-resolution X-ray and/or NMR structures of representative members of every enzyme in the type II pathway are now available. The structural biology of these proteins reveals the specific three-dimensional features of the enzymes that explain substrate recognition, chain length specificity, and the catalytic mechanisms that define their roles in producing the multitude of products generated by the type II system. These structures are also a valuable resource to guide antibacterial drug discovery.

The structural biology of type ii fatty acid biosynthesis

Abnormal choline metabolism is emerging as a metabolic hallmark that is associated with oncogenesis and tumour progression. Following transformation, the modulation of enzymes that control anabolic and catabolic pathways causes increased levels of choline-containing precursors and breakdown products of membrane phospholipids. These increased levels are associated with proliferation, and recent studies emphasize the complex reciprocal interactions between oncogenic signalling and choline metabolism. Because choline-containing compounds are detected by non-invasive magnetic resonance spectroscopy (MRS), increased levels of these compounds provide a non-invasive biomarker of transformation, staging and response to therapy. Furthermore, enzymes of choline metabolism, such as choline kinase, present novel targets for image-guided cancer therapy.

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Choline metabolism in malignant transformation

2,5-Diketopiperazines: synthesis, reactions, medicinal chemistry, and bioactive natural products.

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

Structure of Sch 68631: A new hepatitis C virus proteinase inhibitor from Streptomyces sp.

Four novel platelet activating factor (PAF) antagonists, Sch 47918, Sch 49026, Sch 49027 and Sch 49028, were isolated from the fermentation broth of the fungal culture, Phoma sp. (ATCC 74077). The structures of these compounds were elucidated by spectroscopic methods. The structure and stereochemistry of the first isolated component, Sch 47918, were confirmed by single crystal X-ray diffraction analysis. Sch 49028, the most active component, was found to inhibit PAF-induced human platelet aggregation in vitro with an IC50 of 1.26 μM. However, this compound was inactive in vivo at 5 mg/kg, iv against PAF-induced bronchospasm in guinea pigs.

A novel class of platelet activating factor antagonists from Phoma sp.

Sch 52900 (1) and Sch 52901 (2), two new inhibitors of c-fos proto-oncogene induction, have been isolated from the fermentation of broth of the fungal culture (SCF-1168), Gliocladium sp. Along with compounds 1 and 2, a known compound verticillin A (3) was also obtained from the culture. Structure elucidation of 1 and 2, accomplished by analysis of spectral data in comparison with the data of 3, revealed both 1 and 2 were found to be closely related to the verticillin family of diketopiperazines. All three compounds prevented serum-stimulated transcription of the human c-fos promoter, using a fos/lac Z reporter gene assay, with IC50 values of 1.5, 18 and 0.5 microM of 1, 2 and 3, respectively. Northern analysis revealed the exposure of cells to compound 3 causes inhibition of both phorbol ester-induced c-fos induction of serum-induced JE induction in the absence of inhibiting RNA synthesis, as measured by [3H]uridine incorporation. There results suggest that this class of compounds exerts antitumor activity by blocking a signal transduction pathway that is common to and necessary for the induction of at least a subset of immediate early genes involved in cell proliferation.

Inhibition of c-fos proto-oncogene induction by Sch 52900 and Sch 52901, novel diketopiperazines produced by Gliocladium sp.

A novel class of antitumor metabolites from the fungus Nattrassia Mangiferae

A novel platelet activating factor (PAF) antagonist, Sch 47918, was isolated from the fermentation broth of the fungus, Phoma sp. The structure of this compound was elucidated by spectroscopic methods. The proposed structure and stereochemistry of Sch 47918 were confirmed by single-crystal X-ray diffraction analysis. Sch 47918 was found to be active at IC 50 =6.96 μM in the in vitro PAF-induced human platelet aggregation assay

Min Chu

Papers

Structure of Sch 68631: A new hepatitis C virus proteinase inhibitor from Streptomyces sp.

A novel class of platelet activating factor antagonists from Phoma sp.

Inhibition of c-fos proto-oncogene induction by Sch 52900 and Sch 52901, novel diketopiperazines produced by Gliocladium sp.

A novel class of antitumor metabolites from the fungus Nattrassia Mangiferae

Sch 47918: A novel PAF antagonist from the fungus Phoma sp