Symbiotic Actinomycetes are known to produce a plethora of natural products of pharmacological importance and global genome sequencing efforts unraveled their unique and still mostly untapped biosynthetic potential. To activate natural product biosynthesis in Actinobacteria and to harvest the wealth of natural products, cultivation conditions mimicking the natural environment turned out to be amongst the most promising approach next to molecular biotechnological tools. We have recently applied ecology-driven interaction studies between bacterial symbionts of fungus-farming termites and their natural antagonists to activate the biosynthetic repertoire of actinomycetous symbionts. In light of these studies, we revisited the bacterial symbiont Streptomyces sp. M56 (from now on named M56), which showed very strong antagonistic effect against parasitic co-isolated fungi and was found to produce, not only the ansamycin-derived natural products natalamycin and geldanamycin, but also elaiophylins and the structurally related efomycins.
Our group thoroughly investigated culture extracts obtained from strain M56 by liquid chromatography/high resolution tandem mass spectrometry (LC-HRMS2) and Global Natural Product Social Molecular Networking (GNPS) analysis. Indeed, dereplication of the acquired MS2 data based on available databases resulted in the detection of several polyhydroxylated macrolides identified as the antifungal azalomycins (Figure 1). Although the planar structures of azalomycins were reported as early as 1959 and the first skeletal structure assigned already in 1982, reports on their absolute structures remained inconclusive with varying structural assignments across the literature (Figure 2).
Due to their strong antimicrobial activity, but inconclusive structural assignments, we re-evaluated the analytical and bioactivity data of azalomycins. Here, we provide a conclusive analysis of their stereochemical assignment based on comparative NMR and gene clusters studies and propose to partially revise the absolute structures and names of azalomycins from previous reports (Figure 3).
Ki Hyun Kim is associate professor in the School of Pharmacy at the Sungkyunkwan University (Republic of Korea). He earned his pharmacist’s license in 2005 and he received his PhD in the School of Pharmacy at the Sungkyunkwan University in 2011. From 2011 to 2012 he did postdoctoral studies at the School of Pharmacy at the Sungkyunkwan University, and from 2012 to 2013 at Harvard University and Harvard Medical School. He started his faculty in the School of Pharmacy at the Sungkyunkwan University in 2014. The main research field of Professor Kim is the discovery of the secondary metabolites from diverse natural resources including wild mushrooms, insect-associated bacteria, marine natural sources and medicinal plants and his group has substantial experience and expertise in natural product isolation and structural elucidation using mainly NMR-based analysis as well as biological activity evaluations. He is the author of 7 patents and more than 300 articles indexed by SCIE and cited more than 1500 times with an index H = 20.