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Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 462049, 10 pages
http://dx.doi.org/10.1155/2012/462049
Review Article

Artificial Chromosomes to Explore and to Exploit Biosynthetic Capabilities of Actinomycetes

Department of Science and Molecular and Biomolecular Technology, University of Palermo, Viale delle Scienze, 90128 Palermo, Italy

Received 5 April 2012; Revised 20 June 2012; Accepted 4 July 2012

Academic Editor: Jozef Anné

Copyright © 2012 Rosa Alduina and Giuseppe Gallo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Actinomycetes are an important source of biologically active compounds, like antibiotics, antitumor agents, and immunosuppressors. Genome sequencing is revealing that this class of microorganisms has larger genomes relative to other bacteria and uses a considerable fraction of its coding capacity (5–10%) for the production of mostly cryptic secondary metabolites. To access actinomycetes biosynthetic capabilities or to improve the pharmacokinetic properties and production yields of these chemically complex compounds, genetic manipulation of the producer strains can be performed. Heterologous expression in amenable hosts can be useful to exploit and to explore the genetic potential of actinomycetes and not cultivable but interesting bacteria. Artificial chromosomes that can be stably integrated into the Streptomyces genome were constructed and demonstrated to be effective for transferring entire biosynthetic gene clusters from intractable actinomycetes into more suitable hosts. In this paper, the construction of several shuttle Escherichia coli-Streptomyces artificial chromosomes is discussed together with old and new strategies applied to improve heterologous production of secondary metabolites.