Natural products, such as antibiotics, rarely possess properties that make them directly applicable as drugs for human use. Most often, antibiotics must be modified in order to reduce their toxicity, increase solubility and improve stability, etc.
Traditionally, these modifications have been achieved through chemical synthesis. However, some of the chemical groups, especially on complex molecules such as polyketides and peptides, which often possess strong antimicrobial and anticancer properties, are not accessible for modifications by the methods of synthetic chemistry.
An alternative approach, based on interference with the pathway by which these compounds are synthesized in certain microorganisms, opens completely new possibilities for modifications of ‘chemically inaccessible’ groups. This so-called “engineered biosynthesis” allows precise alterations in microbial genes, which lead to predictable changes in the final structure of the natural product.
Implementation of this approach requires solid knowledge about the biochemistry of antibiotic biosynthesis, the availability of biosynthetic genes, the ability to genetically manipulate antibiotic-producing organisms and good knowledge.