Systems biology of antibiotic production by microorganisms

Abstract

The synthesis of secondary metabolites by microorganisms, specifically antibiotics, is of great scientific and economic importance. The onset (control and regulation) of secondary metabolite formation has and still is intriguing scientists both in industry and academia. Despite many studies, there is little known about the molecular mechanisms underlying the regulation of secondary metabolism. With the recent developments in genomics and further development of advanced post-genomic techniques, it will be possible to apply a more holistic analysis to the regulation of antibiotic production in microorganisms. Here we review current knowledge about the control and regulation of secondary metabolites, with a focus on antibiotics. We will also review developments in the genomics of antibiotic-producing microorganisms, and discuss the use of systems biology for gaining a better understanding of the networks involved in regulation of antibiotic production.

Carbon source regulation of antibiotic production

“…A flux increase in the biosynthetic pathway can be improved by directed mutagenesis to elevate precursor availability or reduce by-product formation. 193 For instance, by cloning acetylCoA carboxylase into an expression vector and introducing it into a wild-type strain of S. coelicolor, the conversion of acetyl-CoA into malonyl-CoA was enhanced and channeled to actinorhodin production. 194 In a similar work, deletion of the pfkA2 gene, corresponding to one of the three reported homologs of phosphofructokinase in S. coelicolor, increased actinorhodin and undecylprodigiosin production approximately four times as compared with the wild-type strain.…”

A Comparative Metabolomics Analysis ofSaccharopolyspora spinosaWT, WH124, and LU104 Revealed Metabolic Mechanisms Correlated with Increases in Spinosad Yield

“…1,23) In this study, the biomass and the yield of the spinosad of WH124 were higher than that of wild-type strain. The growth rate of WH124 was faster than that of the WT strain, which means that the fermentation time decreased (Fig.…”

Reverse biological engineering of hrdB to enhance the production of avermectins in an industrial strain of Streptomyces avermitilis

“…Random mutagenesis and screening has traditionally been used for strain improvement as it is technically simple to perform and little knowledge is needed about the strains. With these methods, the productivity of a penicillin strain used in industry was improved by 100,000-fold compared with the original Fleming strain (5). Even though a tremendous increase in production has been achieved, there are certain drawbacks.…”