Microbes have been prolific producers of natural products because of their fast growth rates, scaling-up capability, and efficient genetic manipulation systems. However, in many cases, the production of the favorable metabolites is controlled by specific biosynthetic gene clusters, in competition with their primary metabolism and normal growth. Besides, the regulation of secondary metabolism can be fundamentally distinct among different microbial types and even strains. Although fermentation conditions have been extensively explored and applied to promote productivity, little is known about how these microorganisms adjusted and switched between different metabolic pathways, and our ability to enhance the secondary metabolite production at the molecular level is still limited.
To promote the microbial ability to synthesize more desired compounds, regulations can be achieved intra-, inter-, and extracellularly. Underlying mechanisms need to be elucidated and applied to trigger the metabolic switch. One recent effort increased productivity by engineering the cells to secrete a molecule responsible for the quorum-sensing system. Studies have found that the control of pathways branching off from the same precursors, and molecules inhibiting the biosynthetic pathway can also have benefits. Metabolic switching is nutrient dependent as well which can thus be used as a tool for the induction of secondary metabolites. With the advances in whole genome sequencing and gene annotations, computational modeling of the cellular metabolic network can be built to assist the investigation of metabolic fluxes and the optimization process.
• The investigation of metabolic switch induction by intra- or extracellular signaling affecting the productivity
• The identification of transcription factors responsible for secondary metabolite biosynthesis
• The construction of the metabolic network for target prediction to promote the secondary metabolism
• The study of key enzymes or transporters for diverting intermediates into different metabolic pathways
• The study of mechanism and signal controls of cell growth and secondary metabolite biosynthesis
• The characterization of small molecules as informational cues to regulate gene expression, for example, those associated with sporulation, quorum sensing, catabolic repression, anabolic repression, etc.
Microbes have been prolific producers of natural products because of their fast growth rates, scaling-up capability, and efficient genetic manipulation systems. However, in many cases, the production of the favorable metabolites is controlled by specific biosynthetic gene clusters, in competition with their primary metabolism and normal growth. Besides, the regulation of secondary metabolism can be fundamentally distinct among different microbial types and even strains. Although fermentation conditions have been extensively explored and applied to promote productivity, little is known about how these microorganisms adjusted and switched between different metabolic pathways, and our ability to enhance the secondary metabolite production at the molecular level is still limited.
To promote the microbial ability to synthesize more desired compounds, regulations can be achieved intra-, inter-, and extracellularly. Underlying mechanisms need to be elucidated and applied to trigger the metabolic switch. One recent effort increased productivity by engineering the cells to secrete a molecule responsible for the quorum-sensing system. Studies have found that the control of pathways branching off from the same precursors, and molecules inhibiting the biosynthetic pathway can also have benefits. Metabolic switching is nutrient dependent as well which can thus be used as a tool for the induction of secondary metabolites. With the advances in whole genome sequencing and gene annotations, computational modeling of the cellular metabolic network can be built to assist the investigation of metabolic fluxes and the optimization process.
• The investigation of metabolic switch induction by intra- or extracellular signaling affecting the productivity
• The identification of transcription factors responsible for secondary metabolite biosynthesis
• The construction of the metabolic network for target prediction to promote the secondary metabolism
• The study of key enzymes or transporters for diverting intermediates into different metabolic pathways
• The study of mechanism and signal controls of cell growth and secondary metabolite biosynthesis
• The characterization of small molecules as informational cues to regulate gene expression, for example, those associated with sporulation, quorum sensing, catabolic repression, anabolic repression, etc.