Antibiotic biosynthesis following horizontal gene transfer: new milestone for novel natural product discovery?

Abstract

Bacteria obtain a significant proportion of their genetic diversity via acquisition of DNA from distantly related organisms, a phenomenon known as horizontal gene transfer. The focus of horizontal gene transfer investigations has been primarily on the impact of this phenomenon on the ecological and/or pathogenic characteristics of bacterial species, with very little effort devoted to investigating horizontal gene transfer as a means of drug discovery. Here, we describe a novel approach to harness the power of horizontal gene transfer to produce novel chemotherapeutic molecules, a process that is easily scalable. We describe the state of the art in this field and discuss the current limiting factors associated with this phenomenon. Utilising a horizontal gene transfer method, we have identified and characterised a novel antimicrobial compound. Production of this antibiotic, termed rhodostreptomycin, is associated with the transfer of DNA from a species of Streptomyces to Rhodococcus by an as yet identified mechanism. We believe that horizontal gene transfer may represent the future of natural product discovery and engineering.

Keywords::

• antibiotic
• drug discovery
• horizontal gene transfer
• natural product

Acknowledgements

We thank PA Lessard and C Rha for scientific support and AR Weiz for technical assistance. The gift of a wild-type R. fascians DDO356 strain by the DuPont Co. is acknowledged.

Notes