Discovery of Antibacterials and Other Bioactive Compounds from Microorganisms — Evaluating Methodologies for Discovery and Generation of Non-Ribosomal Peptide Antibiotics

K.      Witting; R.      D. Sussmuth

Abstract

After decades of neglect in industrial research the comeback of natural products is due since improved screening approaches are at disposal, yielding a multitude of new compounds from natural sources. Besides traditional compound libraries peptides are characterized by an enormous structural complexity, thus increasing the chance of finding a hit in a screening. Emphasizing antibacterial compounds structural complexity is a prerequisite for their success.

This review focuses on the screening approaches employed for the discovery of mostly antibacterial, non-ribosomal peptides derived from natural sources. Traditional screening methodologies as well as genetic approaches are discussed in this context. Utilizing genetic engineering methods e.g., precursor-directed biosynthesis, mutasynthesis, combinatorial biosynthesis, as well as chemoenzymatics to achieve greater structural diversity is thoroughly discussed and exemplified by recent discoveries.

Keywords: Antibacterials, peptides, screening approaches, genetic engineering, chemical screening, combinatorial biosynthesis, mutasynthesis, precursor-directed biosynthesis, Bioactive Compounds, Microorganisms