Under starvation conditions myxobacteria form multicellular fruiting bodies in which vegetative cells differentiate into heat- and desiccation-resistant myxospores. Myxobacteria in general are a rich source of secondary metabolites that often exhibit biological activities rarely found in nature. Although the involvement of a yellow compound in sporulation and fruiting body formation of Myxococcus xanthus was described almost 30 years ago, the chemical principle of the pigment remained elusive. This work presents the isolation and structure elucidation of a unique class of pigments that were named DKxanthenes (DKX). The corresponding biosynthetic gene cluster was identified, and DKX-negative mutants were constructed to investigate the physiological role of DKX during development. In these mutants, fruiting body formation was delayed. Moreover, severely reduced amounts of viable spores were observed after 120 h of starvation, whereas no viable spores were formed at all after 72 h. The addition of purified DKX to the mutants resulted in the formation of viable spores after 72 h. Even though an antioxidative activity could be assigned to DKX, the true biochemical mechanism underlying the complementation remains to be elucidated.

The anti-fungal leupyrrins are secondary metabolites produced by several strains of the myxobacterium Sorangium cellulosum. These intriguing compounds incorporate an atypically substituted γ-butyrolactone ring, as well as pyrrole and oxazolinone functionalities, which are located within an unusual asymmetrical macrodiolide. Previous feeding studies revealed that this novel structure arises from the homologation of four distinct structural units, nonribosomally-derived peptide, polyketide, isoprenoid and a dicarboxylic acid, coupled with modification of the various building blocks. Here we have attempted to reconcile the biosynthetic pathway proposed on the basis of the feeding studies with the underlying enzymatic machinery in the S. cellulosum strain So ce690. Gene products can be assigned to many of the suggested steps, but inspection of the gene set provokes the reconsideration of several key transformations. We support our analysis by the reconstitution in vitro of the biosynthesis of the pyrrole carboxylic starter unit along with gene inactivation. In addition, this study reveals that a significant proportion of the genes for leupyrrin biosynthesis are located outside the core cluster, a ‘split’ organization which is increasingly characteristic of the myxobacteria. Finally, we report the generation of four novel deshydroxy leupyrrin analogues by genetic engineering of the pathway.