Lavasamycins – new natural products from bacteria

New bacterial strains as a source of antibiotics

Bacteria of the genus Streptomyces produce an enormous variety of natural compounds, including antibiotics. Phylogenetically closely related bacterial strains often produce similar secondary metabolites. Therefore, investigating strains that differ in their phylogenetic relationships from known producers can be a useful strategy in the search for new natural products. The DSMZ’s microbial resource collection provides an important foundation for this research: it preserves characterized microorganisms that have not yet been comprehensively investigated for their potential to produce natural products, including antibiotics.

Discovery of two lavasamycins

The researchers isolated two previously unknown natural products from the newly characterized strain Streptomyces barkulensis subsp. lavasanensis, naming them lavasamycin A and B. Both belong to the class of anthraquinone derivatives and contain an unusual sugar moiety. Lavasamycin B also features a rare structural element known as a butenolide unit. In laboratory tests, lavasamycin A inhibited the growth of the Gram-positive bacterium Bacillus subtilis, whereas no such activity was observed for lavasamycin B under the conditions tested. The structural features and differing biological activities of the two compounds make them interesting additions to the diversity of microbial natural products and provide a basis for further investigations into their biosynthesis and properties.

Characterization of the biosynthetic gene cluster

In addition to the chemical analysis, the team investigated the genetic basis of lavasamycin production. The researchers experimentally confirmed the biosynthetic gene cluster responsible for producing the compounds, a type II polyketide synthase cluster, and demonstrated that a repressor inhibits their production. Inactivating this regulator led to a substantial increase in lavasamycin production. These findings provide insights into the regulatory mechanisms underlying lavasamycin biosynthesis and demonstrate how production levels can be influenced through targeted genetic modifications.

Collaboration advancing natural product research

“The combination of taxonomic characterization, natural product chemistry and targeted genetic investigations enables us to discover new natural products, including antibiotics, and to better understand their biosynthesis. Our study also highlights the potential of previously underexplored Streptomyces strains for natural product research,” says Prof. Yvonne Mast, Interim Scientific Director of the Leibniz Institute DSMZ and Head of the Department Bioresources for Bioeconomy and Health Research.

BACKGROUND: Nature’s chemical factories – the genus Streptomyces

• Microbial powerhouses: Bacteria of the genus Streptomyces belong to the actinomycetes and are found predominantly in soil. They are characterized by complex, fungus-like growth, forming filamentous networks known as mycelia.
• Producers of medicinal compounds: More than half of the naturally derived antibiotics currently used in medicine, including streptomycin, tetracycline and erythromycin, are produced by streptomycetes. This group of bacteria also produces numerous other medically important compounds, including anticancer drugs and immunosuppressants such as rapamycin.
• Genetic biosynthetic potential: The genomes of streptomycetes contain numerous biosynthetic gene clusters responsible for producing natural compounds. Genome mining enables researchers to identify these clusters and gain insights into which natural products microorganisms may be capable of producing. Targeted genetic modifications, known as genetic engineering, also make it possible to investigate biosynthetic pathways and their regulation experimentally and to influence the production of specific natural products. Together, these approaches open up new opportunities to explore the diversity of microbial natural products and better understand how they are produced.