Specialised metabolites regulating antibiotic biosynthesis in Streptomyces spp.
Streptomyces bacteria are the major source of antibiotics and other secondary metabolites. Various environmental and physiological conditions affect the onset and level of production of each antibiotic by influencing concentrations of the ligands for conserved global regulatory proteins. In addition, as reviewed here, well-known autoregulators such as γ-butyrolactones, themselves products of secondary metabolism, accumulate late in growth to concentrations allowing their effective interaction with cognate binding proteins, in a necessary prelude to antibiotic biosynthesis. Most autoregulator binding proteins target the conserved global regulatory gene adpA, and/or regulatory genes for 'cluster-situated regulators' (CSRs) linked to antibiotic biosynthetic gene clusters. It now appears that some CSRs bind intermediates and end products of antibiotic biosynthesis, with regulatory effects interwoven with those of autoregulators. These ligands can exert cross-pathway effects within producers of more than one antibiotic, and when excreted into the extracellular environment may have population-wide effects on production, and mediate interactions with neighbouring microorganisms in natural communities, influencing speciation. Greater understanding of these autoregulatory and cross-regulatory activities may aid the discovery of new signalling molecules and their use in activating cryptic antibiotic biosynthetic pathways.
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Guoqing
G
Niu
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich, UK.
Keith F
KF
Chater
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Yuqing
Y
Tian
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Jihui
J
Zhang
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Huarong
H
Tan
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008024:Ligands; D056265:Microbial Interactions / Q000502:physiology*; D011485:Protein Binding; D015398:Signal Transduction; D013302:Streptomyces / Q000235:genetics / Q000502:physiology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008024:Ligands
Streptomyces; antibiotic biosynthesis; interspecies communication; regulation; signalling molecules; γ-butyrolactones