MbtH-like proteins: from enigmatic bystanders to key players in bacterial nonribosomal peptide biosynthesis

Nonribosomal peptides (NRPs) are a class of small molecules that are renowned for their tremendous structural diversity. They are mainly produced by bacteria and filamentous fungi, and while the function of these molecules for the producing organisms remains unclear in most instances, there is evidence that some NRPs serve as virulence factors for pathogenic microbes, and some exhibit toxic effects in humans and animals when ingested. Furthermore, many NRPs have useful applications in human and veterinary medicine as antibacterial, antifungal, anthelmintic, antitumor and immunosuppressive agents, and in agriculture as herbicidal compounds. The biosynthetic genes for producing NRPs are usually arranged in large clusters in the genomes of the producing organisms. These clusters contain the genes encoding the large, multienzyme machines that produce the NRP backbone, along with genes responsible for the synthesis of building blocks, product modification, self-resistance and product export. In addition, many (but not all) bacterial NRP gene clusters harbour a small gene encoding a member of the MbtH-like protein family, which is named for the MbtH protein encoded in the mycobactin biosynthetic gene cluster in Mycobacterium tuberculosis. The function of these proteins has remained a mystery for many years, but recent research has begun to shed light on their importance for NRP biosynthesis. This seminar will discuss our current knowledge of the role of MbtH-like proteins in bacterial NRP production, and will include results from our own research on an MbtH-like protein involved in the biosynthesis of a virulence-associated phytotoxin by the economically important plant pathogen Streptomyces scabiei.