Bumpus Stefanie B, Kelleher Neil L
Department of Chemistry & The Institute for Genomic Biology, University of Illinois Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
Curr Opin Chem Biol. 2008 Oct;12(5):475-82. doi: 10.1016/j.cbpa.2008.07.022.
Two important classes of natural products are made by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). With most biosynthetic intermediates covalently tethered during biogenesis, protein mass spectrometry (MS) has proven invaluable for their interrogation. New mass spectrometric assay formats (such as selective cofactor ejection and proteomics style LC-MS) are showcased here in the context of functional insights into new breeds of NRPS/PKS enzymes, including the first characterization of an 'iterative' PKS, the biosynthesis of the enediyne antitumor antibiotics, the study of a new strategy for PKS initiation via a GNAT-like mechanism, and the analysis of branching strategies in the so-called 'AT-less' NRPS/PKS hybrid systems. The future of MS analysis of NRPS and PKS biosynthetic pathways lies in adoption and development of methods that continue bridging enzymology with proteomics as both fields continue their post-genomic acceleration.
两类重要的天然产物由非核糖体肽合成酶(NRPS)和聚酮化合物合成酶(PKS)合成。由于大多数生物合成中间体在生物合成过程中通过共价键连接,蛋白质质谱(MS)已被证明对研究它们非常有价值。本文展示了新的质谱分析方法(如选择性辅因子排出和蛋白质组学风格的液相色谱 - 质谱联用)在对新型NRPS / PKS酶的功能洞察方面的应用,包括对“迭代”PKS的首次表征、烯二炔类抗肿瘤抗生素的生物合成、通过类GNAT机制启动PKS的新策略研究以及对所谓“无AT”NRPS / PKS杂交系统中分支策略的分析。NRPS和PKS生物合成途径的质谱分析的未来在于采用和开发能够继续将酶学与蛋白质组学联系起来的方法,因为这两个领域都在继续加速后基因组时代的发展。