An iterative type I polyketide synthase initiates the biosynthesis of the antimycoplasma agent micacocidin.

Micacocidin is a thiazoline-containing natural product from the bacterium Ralstonia solanacearum that shows significant activity against Mycoplasma pneumoniae. The presence of a pentylphenol moiety distinguishes micacocidin from the structurally related siderophore yersiniabactin, and this residue also contributes to the potent antimycoplasma effects. The biosynthesis of the pentylphenol moiety, as deduced from bioinformatic analysis and stable isotope feeding experiments, involves an iterative type I polyketide synthase (iPKS), which generates a linear tetraketide intermediate from acyl carrier protein-tethered hexanoic acid by three consecutive, decarboxylative Claisen condensations with malonyl-coenzyme A.

Characterization of the Suillus grevillei quinone synthetase GreA supports a nonribosomal code for aromatic α-keto acids.

The gene greA was cloned from the genome of the basidiomycete Suillus grevillei. It encodes a monomodular natural product biosynthesis protein composed of three domains for adenylation, thiolation, and thioesterase and, hence, is reminiscent of a nonribosomal peptide synthetase (NRPS). GreA was biochemically characterized in vitro.

Biosynthesis of a complex yersiniabactin-like natural product via the mic locus in phytopathogen Ralstonia solanacearum.

A genome mining study in the plant pathogenic bacterium Ralstonia solanacearum GMI1000 unveiled a polyketide synthase/nonribosomal peptide synthetase gene cluster putatively involved in siderophore biosynthesis. Insertional mutagenesis confirmed the respective locus to be operational under iron-deficient conditions and spurred the isolation of the associated natural product. Bioinformatic analyses of the gene cluster facilitated the structural characterization of this compound, which was subsequently identified as the antimycoplasma agent micacocidin.

Ralfuranone biosynthesis in Ralstonia solanacearum suggests functional divergence in the quinone synthetase family of enzymes.

Ralstonia solanacearum is a destructive crop plant pathogen and produces ralfuranone, i.e., a monophenyl-substituted furanone.

Spotlights on advances in mycotoxin research.

A remarkable feature of filamentous fungi is their ability to produce small yet structurally complex and often bioactive natural products. In this mini-review, we cover advances in the research on fungal secondary metabolites, particularly mycotoxins, and focus on biosynthetic aspects as well as on the complex regulatory mechanisms which control the expression of biosynthetic genes. We also highlight the increasing impact of genomics and transcriptomics, which help explore the realm of secondary metabolism of fungi.