| Autor: |
Sit CS; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;, Ruzzini AC; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;, Van Arnam EB; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;, Ramadhar TR; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115;, Currie CR; Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706., Clardy J; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115; jon_clardy@hms.harvard.edu. |
| Abstrakt: |
Small molecules produced by Actinobacteria have played a prominent role in both drug discovery and organic chemistry. As part of a larger study of the actinobacterial symbionts of fungus-growing ants, we discovered a small family of three previously unreported piperazic acid-containing cyclic depsipeptides, gerumycins A-C. The gerumycins are slightly smaller versions of dentigerumycin, a cyclic depsipeptide that selectively inhibits a common fungal pathogen, Escovopsis. We had previously identified this molecule from a Pseudonocardia associated with Apterostigma dentigerum, and now we report the molecule from an associate of the more highly derived ant Trachymyrmex cornetzi. The three previously unidentified compounds, gerumycins A-C, have essentially identical structures and were produced by two different symbiotic Pseudonocardia spp. from ants in the genus Apterostigma found in both Panama and Costa Rica. To understand the similarities and differences in the biosynthetic pathways that produced these closely related molecules, the genomes of the three producing Pseudonocardia were sequenced and the biosynthetic gene clusters identified. This analysis revealed that dramatically different biosynthetic architectures, including genomic islands, a plasmid, and the use of spatially separated genetic loci, can lead to molecules with virtually identical core structures. A plausible evolutionary model that unifies these disparate architectures is presented. |
