Antibiotics: Biosynthesis, Generation of Novel Compounds

Abstract

Many antibiotics and other bioactive molecules originate from biological sources, mainly bacteria and fungi. In this article, the biosynthetic principles of the three most important classes of antibiotics are discussed and examples of the biotechnological potential of pathway engineering are presented. Polyketides, among them medically important antibacterial drugs like tetracycline or erythromycin, are assembled from basic acyl‐CoA building blocks by a mechanism that is closely related to fatty acid synthesis. Another important group of antibiotics are modified peptides like penicillin or vancomycin which are synthesized by complex modular megaenzymes. These nonribosomal peptide synthetases use proteinogenic as well as nonproteinogenic amino acids as substrates. In addition some other peptide antibiotics, like the lantibiotic nisin which is widely used as a food additive, are synthesized by the cellular ribosomal protein biosynthesis machinery and subsequently modified by specific enzymes. Aminoglycoside antibiotics like streptomycin are assembled from complex sugar or sugar‐like molecules which are specifically synthesized during secondary metabolite production. The elucidation of the molecular machinery of antibiotic biosynthesis enabled technologies that can be used to optimize the secondary metabolites by genetic engineering. In this article, some strategies are highlighted which allow the modification of secondary metabolites in ways that were hard to achieve using only synthetic chemistry approaches.

Actinomycete-Derived Polyketides as a Source of Antibiotics and Lead Structures for the Development of New Antimicrobial Drugs

“…The iterative type I PKS [47,48] work in a similar fashion as the iterative type II PKSs [44]. However, the bacterial iterative type I PKSs only facilitate the biosynthesis of small aromatic polyketides [35,49].…”