Genetic Engineering of Myxobacterial Natural Product Biosynthetic Genes

BRYAN JULIEN, AND EDUARDO RODRIGUEZ

Manual of Industrial Microbiology and Biotechnology: Third Edition

ASM Press

Año: 2010; p. 426 - 437

Plants and microbes have been a rich source of bioactive natural products, some of which have been developed for medical or animal health uses. The importance of natural products is highlighted by the fact that 34% of all small molecule drugs developed over the last 25 years have been derived from natural products or their semi-synthetic derivates. Of the microbes, actinomycetes are the largest known producer of natural products. Recently, myxobacteria have been identified as an alternative source of natural products through the work of the group lead by Dr. Reichenbach at Gesellschaft für Biotechnologische Forschung (GBF). From ~7500 strains of myxobacteria isolated, many novel bioactive compounds have been discovered. Myxobacteria are gram-negative soil bacteria that have the ability to form complex fruiting bodies under adverse environmental conditions, which can be simple mound structures as seen in Myxococcus xanthus or elaborate multi-branched stalked structures as in Chondromyces crocatus. These fruiting bodies house dormant spores that are resistant to many environmental stresses. Natural products produced from myxobacteria have gained wide interest recently. To date, more than 100 new structures and some 500 variants have been identified. The majority of myxobacterial natural products have been isolated from strains of Sorangium cellulosum (48%), Myxococcus (20%) and Chondromyces (10%). Most of these natural products are hybrid molecules consisting of polyketides and non-ribosomally made peptides in a linear or cyclic form. Although the addition of modified sugars to natural products from Streptomyces is common, they are rarely found on myxobacterial natural products. Less common but noteworthy features of myxobacterial natural products are two compounds with chlorinated amino acids, one with a cyclopropane ring, and compounds that complexes with boron. Finally, a few terpenoid compounds have been identified.