This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Natural products produced by microorganisms are a promising source of new drugs. Researchers at the Helmholtz Center for Infection Research (HZI) and its Saarbrücken-based site, the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), have now discovered a new family of such compounds, elucidated their unusual biosynthesis and developed a way to produce them synthetically.
They also found that this class of compounds binds specifically to a human protein involved in the development of cancer. The findings were published in two thematically linked studies in Angewandte Chemie International Edition. The two studies focus on so-called myxoglucamides, which are produced by soil-dwelling myxobacteria.
These bacteria are known for generating a diversity of natural products, many of which show biological activity. In the first study, using modern genetic methods, the team succeeded in specifically activating the biosynthetic pathway for myxoglucamides that had remained silent in the bacteria. This was the key to producing and detecting the compounds in the first place.
What makes myxoglucamides particularly interesting is their unusual structure: They combine building blocks derived from sugars, lipids and amino acids in a way that clearly sets them apart from previously known natural products. HIPS is a site of the Helmholtz Center for Infection Research in collaboration with Saarland University. The researchers also investigated how these molecules are assembled in the bacteria.
To do so, they analyzed the underlying genetic blueprint—the so-called biosynthetic gene cluster—as well as the individual biochemical steps required for myxoglucamide production. Their work revealed a previously unknown biosynthetic pathway. Several enzymes act together in an unexpected way, generating a chemical structure that had not been described before in this form.
The study thus provides new insights into how microorganisms construct complex natural products and how such hidden compounds may be identified more systematically in the future. "The discovery of myxoglucamides highlights how much chemical potential remains hidden in previously silent biosynthetic gene clusters of microorganisms," says Dr. Chengzhang Fu, head of the junior research group "Genome Mining for Secondary Metabolites" at HIPS.
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