Current Techniques For The Search For Natural Products In Actinobacteria
Records of Natural Products
Available Online: October 14,2021
p.1 - 19
http://doi.org/10.25135/rnp.286.2107-2132 (DOI number will be activated after the manuscript has been available in an issue.)
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- Janette Berenice Gonzalez-Nava
- Scarlett Alonso-Carmona
- Gauddy Lizeth Manzanares-Leal
- Horacio Sandoval-Trujillo
- Ninfa Ramírez-Durán
The actinobacteria, also referred to as actinomycetes, have been the most widely used bacteria to produce industrial interest compounds due to their great biosynthetic capacity to generate structural diversity molecules. The actinobacteria with the most significant biosynthetic potential are the genus Streptomyces, Saccharopolyspora, and Micromonospora containing groups of biosynthetic genes such as polyketide synthase systems, non-ribosomal peptide synthase systems, terpenoid systems, ribosomally synthesized and post-translationally modified peptide systems, among others. This review focuses on genomic mining techniques and current helpful software to search for new natural products in actinobacteria. Currently, molecular techniques have been developed to improve the isolation of natural products, and bioinformatics programs, many are free to access, have been designed to analyze genes and microbial genomes that predict new molecule production. Thanks to these techniques, new natural products of industrial interest have been found in rare actinobacteria such as Nocardia and Rhodococcus.KEYWORDS
- Genomic mining
- Natural products
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Figure 1. Conformation of a PKS system
Figure 2. Conformation of a NRPS system
Figure 3. 5C terpenoid precursors and structures derived from the union of two or more precursor molecules will form the skeletons for complex terpenoid molecules.
Figure 4. Diagram of RiPP peptides’ biosynthesis, the modifications are different and complex, resulting in products with molecular diversity
Figure 5. a) Diagram of classical mining development for the search of new natural products. b) Biosynthetic genes are searched using specific primers in a PCR reaction, the amplified genes are sequenced for bioinformatic analysis and prediction of chemical structures
Figure 6. a) Procedure to search for BGCs in bacterial genomes. b) The genome is analyzed with bioinformatics programs to know all the BGCs, the genes of interest are chosen to produce one or more natural products.
Figure 7. a) Procedure for the search of new natural products from phylogenetic techniques. b) Phylogenetic relationships are searched in genomes or groups of BGCs in a group of microorganisms (species or genera); a network analysis of the clusters formed allows finding related groups. The BGCs are compared to predict chemical structures synthesized by the same group of microorganisms
Figure 8. a) Procedure to find new natural compounds by regulation of resistance genes. b) BGCs, and other genes involved in biosynthesis are searched, the set of genes is attached to a vector, heterologous expression can be performed, and other regulatory genes can be integrated, the vector and the set of genes are inserted into the final host. The mutant is grown and reproduced to express the biosynthetic genes
Figure 9. a) Procedure to find new natural compounds by gene regulation. b) BGC and regulatory