A commensal strain of Staphylococcus epidermidis protects against skin neoplasia.

We report the discovery that strains of Staphylococcus epidermidis produce 6-N-hydroxyaminopurine (6-HAP), a molecule that inhibits DNA polymerase activity. In culture, 6-HAP selectively inhibited proliferation of tumor lines but did not inhibit primary keratinocytes. Resistance to 6-HAP was associated with the expression of mitochondrial amidoxime reducing components, enzymes that were not observed in cells sensitive to this compound. Intravenous injection of 6-HAP in mice suppressed the growth of B16F10 melanoma without evidence of systemic toxicity. Colonization of mice with an S. epidermidis strain producing 6-HAP reduced the incidence of ultraviolet-induced tumors compared to mice colonized by a control strain that did not produce 6-HAP. S. epidermidis strains producing 6-HAP were found in the metagenome from multiple healthy human subjects, suggesting that the microbiome of some individuals may confer protection against skin cancer. These findings show a new role for skin commensal bacteria in host defense. Sci Adv 2018 Feb 28; 4(2):eaao450

The chemistry and biology of zoanthamine alkaloids and Illicium sesquiterpenes

Natural products, or secondary metabolites, have proven significant to the existence of life. They have been used for countless reasons throughout history, including nonessential purposes such as dyes for textiles and paints. Less trivial uses, such as those related to health better demonstrate the importance of natural products. Toxic natural products had been used to bolster hunting efficiency and insect pheromones. Therapeutic natural products have long been used as dietary supplements and medicines. The ubiquitous nature of natural products and their derivatives in current medicinal validates continued investigations in all areas of natural product research. Our laboratory has a longstanding tradition in the synthesis and evaluation of biologically interesting natural products. We have viewed natural product synthesis as a tool to expand our understanding of organic chemistry. Of particular are natural products with novel architectures. The synthetic study of these natural products often inspires creativity to solve complicated synthetic challenges, and leads to the development of new methodologies. Novel structural characteristics and attractive bioactivities of two natural product families, zoanthamine alkaloids and Illicium sesquiterpenes, caught our interest for the stated reasons. Research herein describes work directed towards synthesis of the ABC ring system of norzoanthamine, total syntheses of Illicium sesquiterpenes jiadifenolide and jiadifenin. Chapters 1 and 2 narrate the background and research related to the norzoanthamine ABC ring motif. Chapters 3 and 4 report the total syntheses of jiadifenolide and jiadifenin, and their biological studies related to their neurotrophic activit

A commensal strain of Staphylococcus epidermidis protects against skin neoplasia.

We report the discovery that strains of Staphylococcus epidermidis produce 6-N-hydroxyaminopurine (6-HAP), a molecule that inhibits DNA polymerase activity. In culture, 6-HAP selectively inhibited proliferation of tumor lines but did not inhibit primary keratinocytes. Resistance to 6-HAP was associated with the expression of mitochondrial amidoxime reducing components, enzymes that were not observed in cells sensitive to this compound. Intravenous injection of 6-HAP in mice suppressed the growth of B16F10 melanoma without evidence of systemic toxicity. Colonization of mice with an S. epidermidis strain producing 6-HAP reduced the incidence of ultraviolet-induced tumors compared to mice colonized by a control strain that did not produce 6-HAP. S. epidermidis strains producing 6-HAP were found in the metagenome from multiple healthy human subjects, suggesting that the microbiome of some individuals may confer protection against skin cancer. These findings show a new role for skin commensal bacteria in host defense