From Microbial Proteomics to Synthetic Biology: Amycolatopsis balhimycina case

Actinomycetes, filamentous Gram-positive bacteria, are usually exploited as bio-farms naturally producing a wide range of small biologically active metabolites, such as antibiotics, extensively used in medicine, food-industry, chemistry and bio-remediation strategies. The development of high throughput technologies, like proteomics, allows functional genomic studies aimed at shedding light on molecular mechanisms controlling the production of useful compounds and macromolecules. Differential proteomic analyses, performed by using Two Dimensional PolyAcrylamide Gel Electrophoresis (2D- PAGE) coupled to mass spectrometry (MS) procedures, revealed novel links between balhimycin production (a vancomycin-like antibiotic) and metabolic pathway regulation in Amycolatopsis balhimycina DSM5908. In particular, our investigation, performed by combining data from differential proteomic analyses carried-out using wild-type (Wt) and non-producing strains incubated in different growth conditions, showed that antibiotic production is always associated with the up-regulation of either specific enzymes of balhimycin (bal) biosynthetic gene cluster and enzymes related to central carbon metabolism, cell energy and redox balance. Thus this approach suggested new insights to improve fermentation technology strategies and revealed target genes for synthetic biology approaches aimed to improve antibiotic yield production.