Prediction of Transcription Factors and Their Involvement in Regulating Rifamycin Production in Amycolatopsis mediterranei S699

Amycolatopsis mediterranei: A Sixty-Year Journey from Strain Isolation to Unlocking Its Potential of Rifamycin Analogue Production by Combinatorial Biosynthesis

“…Recently, a proteome analysis to understand the role of genes and enzymes (particularly regulation and export of rifamycin B) involved in the production of rifamycin B was performed by using the wild-type rifamycin B producing A. mediterranei S699, DCO34/36 that produces 24-desmethylrifamycin B, and a nonrifamycin producing single crossover (SCO) of strain S699 obtained during the process of homologous recombination . This study published recently , revealed that primary metabolic pathways were significantly downregulated as A. mediterranei S699 moves toward rifamycin B production. The data generated in this study and the information on the regulatory mechanism of rifamycin B already available in the literature reflected that the expression of genes encoding RifQ and RifP is altered in S699 and DCO34/36.…”

“…The results emphasize the active association of TFs in the maintenance of rifamycin synthesis and its export. Thus, Lal and co-workers have delineated 30 unique transcription factors directly involved in regulating rifamycin production and its extracellular export in A. mediterranei S699, 90 and that can be further subjected to genetic manipulation using CRISPR-assisted technology to further improve the production of rifamycins from A. mediterranei.…”

A Combinatorial Approach of High-Throughput Genomics and Mass Proteomics for Understanding the Regulation and Expression of Secondary Metabolite Production in Actinobacteria

“…However, a gap still remained in genetics-based investigations of polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) biosynthetic pathways and understanding of their regulation, interaction, and activity in living systems. To overcome these hurdles, our group attempted strain-specific high-throughput proteomic mining overlapped with genomics using interactomics ( 36 , 37 ). This multi-omic approach was employed to improve the production of 24-desmethylrifamycin-B, which was highly effective against rifampin-resistant strains of the tuberculosis bacterium (RR-TB) but had low yield.…”

“…This multi-omic approach was employed to improve the production of 24-desmethylrifamycin-B, which was highly effective against rifampin-resistant strains of the tuberculosis bacterium (RR-TB) but had low yield. Where the proteomics approach unveiled the expression profile during the rifamycin production at a different timescale and was a major cause of low yield, the interactomics approach helped to uncover the major regulatory hub proteins that were regulating the secondary metabolite production ( 10 , 36 ). These hubs were later targeted to enhance the production of the antibiotic.…”