Zimmermann Michael, Fischbach Michael A
Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, 94158, USA.
Chem Biol. 2010 Sep 24;17(9):925-30. doi: 10.1016/j.chembiol.2010.08.006.
Each year in the United States, infections by methicillin-resistant Staphylococcus aureus (MRSA) are responsible for ∼19,000 deaths and result in $3-$4 billion of health care costs. Because skin colonization is a major risk factor for S. aureus infection, identifying novel small molecules produced by S. aureus can lead to new molecular insights into its ability to colonize and infect the host and new targets for antibacterial intervention. Here, we report that a nonribosomal peptide synthetase conserved across S. aureus and other skin-associated staphylococci encodes a family of three pyrazinone natural products. These molecules likely result from the synthesis and release of a dipeptide aldehyde, its spontaneous cyclization to a dihydropyrazinone, and subsequent oxidation to a pyrazinone. As an unexpected family of small molecule natural products from the pathogen S. aureus, the pyrazinones may open a new window into the interspecies interactions that underlie the poorly understood process of skin colonization.
在美国，每年耐甲氧西林金黄色葡萄球菌（MRSA）感染导致约19000人死亡，产生30亿至40亿美元的医疗费用。由于皮肤定植是金黄色葡萄球菌感染的主要危险因素，鉴定金黄色葡萄球菌产生的新型小分子能够带来关于其定植和感染宿主能力的新分子见解以及抗菌干预的新靶点。在此，我们报告一种在金黄色葡萄球菌和其他皮肤相关葡萄球菌中保守的非核糖体肽合成酶编码一个由三种吡嗪酮天然产物组成的家族。这些分子可能源于二肽醛的合成与释放、其自发环化形成二氢吡嗪酮以及随后氧化为吡嗪酮。作为来自病原体金黄色葡萄球菌的一类意想不到的小分子天然产物，吡嗪酮可能为理解甚少的皮肤定植过程所基于的种间相互作用打开一扇新窗口。
