期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：43
页码：13150-13154
DOI：10.1073/pnas.1515348112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceBacterially produced natural products comprise a group of molecules with highly diverse and generally complex structures that possess a remarkable array of biological activities. These molecules are separated into families sharing a common structural core and, accordingly, conserved sets of genes encoding the biosynthetic enzymes required to generate these shared structural features. Genomic characterization of related bacteria that produce remarkably similar molecules led to the surprising discovery that gene context was not conserved for the respective biosynthetic pathways. A comparison of these variable arrangements documents one way in which closely related symbiotic bacteria acquire the capacity to produce new molecules with new functions. 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.
关键词：symbiosis ; chemical ecology ; horizontal gene transfer ; biosynthetic gene clusters ; natural products
