Genetic Manipulation of Myxobacteria

WESLEY P. BLACK, BRYAN JULIEN, EDUARDO RODRIGUEZ, AND ZHAOMIN YANG

Manual of Industrial Microbiology and Biotechnology, Third Edition

ASM Press

Año: 2010; p. 262 - 272

Myxobacteria, a coherent group of the delta proteobacteria, are recognized as important producers of secondary metabolites of industrial and medical importance. These Gram-negative bacteria have fascinated scientists for over half a century because of their surface gliding motility and their starvation-induced muticellular development. In more recent years, they have emerged as prominent producers of secondary metabolites. Myxobacteria as a group produce the most bioactive compounds among Gram-negatives and rank 3rd among bacteria, only behind actinomycetes and bacilli. Currently there are over 100 different known structures of natural products from myxobacteria with about 500 structural variants. Sorangium cellulosum accounts for nearly 50% of these and Myxococcus and Stigmatella account for about 25%. What is even more exciting is that the bioactive chemicals from myxobacteria tend to be novel and distinct. For example, S. cellulosum produce epothilones, one of which is currently marketed as an anti-cancer drug (Ixempra® by Bristol-Myers Sqiubb). Although epothilones act as a microtubule stabilizer like paclitaxel, they remain effective against paclitaxel-resistant cancer cells. Genome sequences of a few myxobacteria indicated that there are genes for the biosynthesis of unidentified secondary metabolites. Considering the need for development of new molecules for treatment of a variety of diseases, it is imperative to further explore myxobacteria in industrial microbiology and biotechnology. Genetic manipulations play important roles in identifying and optimally producing secondary metabolites, and myxobacteria are no exception. Luckily, genetic tools for myxobacteria have been developed and perfected over the years. Various schemes of mutagenesis can be applied to myxobacteria. Also applicable are transduction, conjugation and transformation. There are developments that have enabled heterologous gene expression in myxobacteria. These include the construction and development of regulated promoters as well as identification of strong constitutive promoters. Recently, the first autonomously replicating plasmid has been identified. While most of the tools were first developed for the model myxobacterium Myxococcus xanthus, many have been applied to S. cellulosum, Stigmatella aurantiaca, and to the lesser known myxobacteria Chondromyces crocatus, Cystobacter fuscus, Angiococcus disciformis, and Corallococcus macrosporus . The stage is now set for substantial improvement of myxobacteria for use in biotechnology using the tools that are the focus of this chapter.