Natural products (NPs) play vital roles in drug discovery and development, especially being applied as antibiotics. In recent years, there has been a sharp increase in multidrug-resistant pathogens, leading to a rapid growth of demand for new NPs and their chemical derivatives for antimicrobial drug development. In addition to chemical total synthesis and diversity-oriented chemical synthesis that aims to produce NP-like chemical libraries, genome mining has been widely used in recent decades to identify novel biosynthetic gene clusters (BGCs) for NP production. These BGCs can meet the constant demand for new chemical entities. In general, there are far more BGCs embedded in microbial genomes than the number of NPs produced in laboratories. As a result, a range of approaches, such as promoter substitution and heterologous expression, have been developed to activate or trigger these cryptic BGCs to access their hidden chemical diversities.
Typically, the biological activities of organic substances are determined by their chemical structures. Although antimicrobials encompass a wide variety of structural motifs, their biosynthetic logic is often highly conserved and can be assigned to several major classes, including polyketides, nonribosomally synthesized peptides (NRPs), ribosomally synthesized and post-translationally modified peptides (RiPPs), terpenoids, and alkaloids. Understanding the biosynthetic mechanisms of diverse metabolic pathways is vital to create novel genetic combinations of biosynthetic genes and thus generating “unnatural” natural molecules in the future, so-called combinatorial biosynthesis attempts. Nowadays, advances and rapid developments in genome sequencing technologies, bioinformatics, and chemical analysis have accelerated the process of genomics-based discovery for previously overlooked natural products. Besides the well-known producers such as bacteria, fungi, and plants, antimicrobial production can also be explored in neglected anaerobic bacteria or other organisms. Further investigation of antimicrobial production in their native communities will not only provide a deeper understanding of their ecological functions but will also lead to the discovery of new antimicrobials.
This research topic focuses on the identification and structural diversification of novel antimicrobials, as well as the study of their mechanisms. Different types of manuscripts will be considered, with the lists of topics, but are not limited to:
1) Discovery of antimicrobials based on bioactivity-guided approaches
2) Discovery of antimicrobials by genomics-based discovery approaches
3) Structural diversification of antimicrobials by synthetic biology or chemo-enzyme approaches
4) Discovery of bioactive antimicrobials by diversity-oriented chemical synthesis
5) Biosynthetic study of antimicrobials
6) Identification of the action and resistance mechanisms of antimicrobials
Natural products (NPs) play vital roles in drug discovery and development, especially being applied as antibiotics. In recent years, there has been a sharp increase in multidrug-resistant pathogens, leading to a rapid growth of demand for new NPs and their chemical derivatives for antimicrobial drug development. In addition to chemical total synthesis and diversity-oriented chemical synthesis that aims to produce NP-like chemical libraries, genome mining has been widely used in recent decades to identify novel biosynthetic gene clusters (BGCs) for NP production. These BGCs can meet the constant demand for new chemical entities. In general, there are far more BGCs embedded in microbial genomes than the number of NPs produced in laboratories. As a result, a range of approaches, such as promoter substitution and heterologous expression, have been developed to activate or trigger these cryptic BGCs to access their hidden chemical diversities.
Typically, the biological activities of organic substances are determined by their chemical structures. Although antimicrobials encompass a wide variety of structural motifs, their biosynthetic logic is often highly conserved and can be assigned to several major classes, including polyketides, nonribosomally synthesized peptides (NRPs), ribosomally synthesized and post-translationally modified peptides (RiPPs), terpenoids, and alkaloids. Understanding the biosynthetic mechanisms of diverse metabolic pathways is vital to create novel genetic combinations of biosynthetic genes and thus generating “unnatural” natural molecules in the future, so-called combinatorial biosynthesis attempts. Nowadays, advances and rapid developments in genome sequencing technologies, bioinformatics, and chemical analysis have accelerated the process of genomics-based discovery for previously overlooked natural products. Besides the well-known producers such as bacteria, fungi, and plants, antimicrobial production can also be explored in neglected anaerobic bacteria or other organisms. Further investigation of antimicrobial production in their native communities will not only provide a deeper understanding of their ecological functions but will also lead to the discovery of new antimicrobials.
This research topic focuses on the identification and structural diversification of novel antimicrobials, as well as the study of their mechanisms. Different types of manuscripts will be considered, with the lists of topics, but are not limited to:
1) Discovery of antimicrobials based on bioactivity-guided approaches
2) Discovery of antimicrobials by genomics-based discovery approaches
3) Structural diversification of antimicrobials by synthetic biology or chemo-enzyme approaches
4) Discovery of bioactive antimicrobials by diversity-oriented chemical synthesis
5) Biosynthetic study of antimicrobials
6) Identification of the action and resistance mechanisms of antimicrobials