The potent antibacterial lanthipeptide microvionin, isolated from a culture of Microbacterium arborescens, exhibits a new triamino-dicarboxylic acid moiety, termed avionin, and an unprecedented N-terminal guanidino fatty acid. We identified the corresponding biosynthetic gene cluster and reconstituted central steps of avionin biosynthesis in vitro. Genome mining and isolation of nocavionin from Nocardia terpenica revealed a widespread distribution of this lanthipeptide class, termed lipolanthines, which may be useful as future antimicrobial drugs.

BackgroundUstilaginaceae (belonging to the smut fungi) are commonly known for their plant pathogenicity. Although these microbes lead to yield reduction of cereal production, they can also have an economically positive side. Ustilaginaceae naturally produce a versatile range of value-added chemicals with potential applications in the food, pharmaceutical, and chemical industry.ResultsIn this study 68 Ustilaginaceae of 13 species were screened for the production of organic acids, polyols, and glycolipids from glucose to characterize their biodiversity and identify potential novel strains for biocatalysis of these valuable chemicals. Ustilago cynodontis, Ustilago maydis, Ustilago avenae, and Sporisorium exsertum were identified as promising production organisms for itaconate, malate, succinate, and erythritol, respectively. The influence of buffer concentration (pH) on acid production was investigated. Selected strains with best itaconate and malate production were characterized in more detail in bioreactor experiments obtaining total acid concentrations of up to 47 ± 1 g L−1.ConclusionThe identification and detailed characterization of these producers of valuable chemicals highlights the potential of these unicellular smut fungi for industrial applications and is a further step towards the biotechnological utilization of Ustilaginaceae.Electronic supplementary materialThe online version of this article (doi:10.1186/s40694-014-0002-y) contains supplementary material, which is available to authorized users.

Natural products and their semisynthetic derivatives are an important source of drugs for the pharmaceutical industry. Bacteria are prolific producers of natural products and encode a vast diversity of natural product biosynthetic gene clusters. However, much of this diversity is inaccessible to natural product discovery. Here, we use a combination of phylogenomic analysis of the microviridin biosynthetic pathway and chemo-enzymatic synthesis of bioinformatically predicted microviridins to yield new protease inhibitors. Phylogenomic analysis demonstrated that microviridin biosynthetic gene clusters occur across the bacterial domain and encode three distinct subtypes of precursor peptides. Our analysis shed light on the evolution of microviridin biosynthesis and enabled prioritization of their chemo-enzymatic production. Targeted one-pot synthesis of four microviridins encoded by the cyanobacterium Cyanothece sp. PCC 7822 identified a set of novel and potent serine protease inhibitors, the most active of which had an IC value of 21.5 nM. This study advances the genome mining techniques available for natural product discovery and obviates the need to culture bacteria.

Marine sponges are prolific sources of unique bioactive natural products. The sponge is represented by several distinct variants with largely nonoverlapping chemistry. For the Japanese chemotype Y harboring diverse complex polyketides and peptides, we previously provided genomic and functional evidence that a single symbiont, the filamentous, multicellular organism " Entotheonella factor," produces almost all of these compounds. To obtain further insights into the chemistry of "Entotheonella," we investigated another phylotype, " Entotheonella serta," present in the WA sponge chemotype, a source of theonellamide- and misakinolide-type compounds. Unexpectedly, considering the lower chemical diversity, sequencing of individual bacterial filaments revealed an even larger number of biosynthetic gene regions than for E. factor, with virtually no overlap. These included genes for misakinolide and theonellamide biosynthesis, the latter assigned by comparative genomic and metabolic analysis of a chemotype from Israel, and by biochemical studies. The data suggest that both compound families, which were among the earliest model substances to study bacterial producers in sponges, originate from the same bacterium in WA. They also add evidence that metabolic richness and variability could be a more general feature of Entotheonella symbionts.