Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, Skaggs School of Pharmacy and Pharmaceutical Sciences, Moores Comprehensive Cancer Center, University of California, La Jolla, San Diego, CA 92093, USA.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, UT 84112, USA.
Mar Drugs. 2023 Jun 20;21(6):367. doi: 10.3390/md21060367.
Marinolides A and B, two new 24- and 26-membered bacterial macrolactones, were isolated from the marine-derived actinobacterium AJS-327 and their stereostructures initially assigned by bioinformatic data analysis. Macrolactones typically possess complex stereochemistry, the assignments of which have been one of the most difficult undertakings in natural products chemistry, and in most cases, the use of X-ray diffraction methods and total synthesis have been the major methods of assigning their absolute configurations. More recently, however, it has become apparent that the integration of bioinformatic data is growing in utility to assign absolute configurations. Genome mining and bioinformatic analysis identified the 97 kb biosynthetic cluster harboring seven type I polyketide synthases. A detailed bioinformatic investigation of the ketoreductase and enoylreductase domains within the multimodular polyketide synthases, coupled with NMR and X-ray diffraction data, allowed for the absolute configurations of marinolides A and B to be determined. While using bioinformatics to assign the relative and absolute configurations of natural products has high potential, this method must be coupled with full NMR-based analysis to both confirm bioinformatic assignments as well as any additional modifications that occur during biosynthesis.
Marinolides A 和 B 是两种新型的 24 元和 26 元细菌大环内酯类化合物，从海洋来源的放线菌 AJS-327 中分离得到，其立体结构最初通过生物信息数据分析进行了分配。大环内酯类化合物通常具有复杂的立体化学，其分配是天然产物化学中最困难的任务之一，在大多数情况下，使用 X 射线衍射方法和全合成是分配其绝对构型的主要方法。然而，最近越来越明显的是，整合生物信息数据对于分配绝对构型变得越来越有用。基因组挖掘和生物信息学分析确定了含有七个 I 型聚酮合酶的 97 kb 生物合成簇。对多模块聚酮合酶中的酮还原酶和烯酰还原酶结构域进行详细的生物信息学研究，结合 NMR 和 X 射线衍射数据，确定了 marinolides A 和 B 的绝对构型。虽然使用生物信息学来分配天然产物的相对和绝对构型具有很高的潜力，但该方法必须与基于 NMR 的全分析相结合，以验证生物信息学的分配，并确认在生物合成过程中发生的任何其他修饰。
