Late-stage diversification of bacterial natural products through biocatalysis
Authors
Lazić, JelenaFilipović, Vuk
Pantelić, Lena
Milovanović, Jelena
Vojnović, Sandra
Nikodinović-Runić, Jasmina
Article (Published version)
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Bacterial natural products (BNPs) have been and still are very important sources of leads for drug development and chemical novelty. The possibility to perform late-stage diversification of these biomolecules is an attractive approach to obtain novel structures by means other than total chemical synthesis or metal complexation reactions. Although biocatalysis is gaining popularity within the context of green chemistry, a vast majority of the sequenced genome data aimed at deciphering metabolic pathways for BNP biosynthesis, possibly containing additional tailoring enzymes, remains underexplored. In this review, we report a systematic overview of biotransformations of 21 molecules, which include derivatization by halogenation, esterification, reduction, oxidation, alkylation and nitration reactions, as well as degradation products as their sub-derivatives. These BNPs were grouped based on their biological activities into antibacterial (5), antifungal (5), anticancer (5), immunosuppressi...ve (2) and quorum sensing modulating (4) compounds. This study summarized 73 derivatives and 16 degradation sub-derivatives originating from 12 BNPs. The remaining 9 BNPs have not been reported as substrates in biotransformation reactions. The highest number of 28 biocatalytic reactions was reported for the antibacterial drug vancomycin, followed by 18 reactions reported for the immunosuppressive drug rapamycin, suggesting that research focus to date was more on BNPs that were already in clinical use. The most common biocatalysts include oxidoreductases, transferases, lipases, isomerases and haloperoxidases. This review highlights biocatalytic routes for the late-stage diversification reactions of BNPs, which potentially help to recognize the structural optimizations of bioactive scaffolds for the generation of new biomolecules, eventually leading to drug development.
Keywords:
bacterial natural products / bioactive molecules / Biocatalysis / Biotransformation / enzymatic diversification / Late-stage modificationSource:
Frontiers in Bioengineering and Biotechnology, 2024, 12Publisher:
- Frontiers
Funding / projects:
- BioECOLogics - Value-added biologics through eco-sustainable routes (RS-ScienceFundRS-Ideje-7730810)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200042 (University of Belgrade, Institute of Molecular Genetics and Genetic Engineering) (RS-MESTD-inst-2020-200042)
URI
https://www.frontiersin.org/articles/10.3389/fbioe.2024.1351583https://imagine.imgge.bg.ac.rs/handle/123456789/2387
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Lazić, Jelena AU - Filipović, Vuk AU - Pantelić, Lena AU - Milovanović, Jelena AU - Vojnović, Sandra AU - Nikodinović-Runić, Jasmina PY - 2024 UR - https://www.frontiersin.org/articles/10.3389/fbioe.2024.1351583 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/2387 AB - Bacterial natural products (BNPs) have been and still are very important sources of leads for drug development and chemical novelty. The possibility to perform late-stage diversification of these biomolecules is an attractive approach to obtain novel structures by means other than total chemical synthesis or metal complexation reactions. Although biocatalysis is gaining popularity within the context of green chemistry, a vast majority of the sequenced genome data aimed at deciphering metabolic pathways for BNP biosynthesis, possibly containing additional tailoring enzymes, remains underexplored. In this review, we report a systematic overview of biotransformations of 21 molecules, which include derivatization by halogenation, esterification, reduction, oxidation, alkylation and nitration reactions, as well as degradation products as their sub-derivatives. These BNPs were grouped based on their biological activities into antibacterial (5), antifungal (5), anticancer (5), immunosuppressive (2) and quorum sensing modulating (4) compounds. This study summarized 73 derivatives and 16 degradation sub-derivatives originating from 12 BNPs. The remaining 9 BNPs have not been reported as substrates in biotransformation reactions. The highest number of 28 biocatalytic reactions was reported for the antibacterial drug vancomycin, followed by 18 reactions reported for the immunosuppressive drug rapamycin, suggesting that research focus to date was more on BNPs that were already in clinical use. The most common biocatalysts include oxidoreductases, transferases, lipases, isomerases and haloperoxidases. This review highlights biocatalytic routes for the late-stage diversification reactions of BNPs, which potentially help to recognize the structural optimizations of bioactive scaffolds for the generation of new biomolecules, eventually leading to drug development. PB - Frontiers T2 - Frontiers in Bioengineering and Biotechnology T1 - Late-stage diversification of bacterial natural products through biocatalysis VL - 12 DO - 10.3389/fbioe.2024.1351583 ER -
@article{ author = "Lazić, Jelena and Filipović, Vuk and Pantelić, Lena and Milovanović, Jelena and Vojnović, Sandra and Nikodinović-Runić, Jasmina", year = "2024", abstract = "Bacterial natural products (BNPs) have been and still are very important sources of leads for drug development and chemical novelty. The possibility to perform late-stage diversification of these biomolecules is an attractive approach to obtain novel structures by means other than total chemical synthesis or metal complexation reactions. Although biocatalysis is gaining popularity within the context of green chemistry, a vast majority of the sequenced genome data aimed at deciphering metabolic pathways for BNP biosynthesis, possibly containing additional tailoring enzymes, remains underexplored. In this review, we report a systematic overview of biotransformations of 21 molecules, which include derivatization by halogenation, esterification, reduction, oxidation, alkylation and nitration reactions, as well as degradation products as their sub-derivatives. These BNPs were grouped based on their biological activities into antibacterial (5), antifungal (5), anticancer (5), immunosuppressive (2) and quorum sensing modulating (4) compounds. This study summarized 73 derivatives and 16 degradation sub-derivatives originating from 12 BNPs. The remaining 9 BNPs have not been reported as substrates in biotransformation reactions. The highest number of 28 biocatalytic reactions was reported for the antibacterial drug vancomycin, followed by 18 reactions reported for the immunosuppressive drug rapamycin, suggesting that research focus to date was more on BNPs that were already in clinical use. The most common biocatalysts include oxidoreductases, transferases, lipases, isomerases and haloperoxidases. This review highlights biocatalytic routes for the late-stage diversification reactions of BNPs, which potentially help to recognize the structural optimizations of bioactive scaffolds for the generation of new biomolecules, eventually leading to drug development.", publisher = "Frontiers", journal = "Frontiers in Bioengineering and Biotechnology", title = "Late-stage diversification of bacterial natural products through biocatalysis", volume = "12", doi = "10.3389/fbioe.2024.1351583" }
Lazić, J., Filipović, V., Pantelić, L., Milovanović, J., Vojnović, S.,& Nikodinović-Runić, J.. (2024). Late-stage diversification of bacterial natural products through biocatalysis. in Frontiers in Bioengineering and Biotechnology Frontiers., 12. https://doi.org/10.3389/fbioe.2024.1351583
Lazić J, Filipović V, Pantelić L, Milovanović J, Vojnović S, Nikodinović-Runić J. Late-stage diversification of bacterial natural products through biocatalysis. in Frontiers in Bioengineering and Biotechnology. 2024;12. doi:10.3389/fbioe.2024.1351583 .
Lazić, Jelena, Filipović, Vuk, Pantelić, Lena, Milovanović, Jelena, Vojnović, Sandra, Nikodinović-Runić, Jasmina, "Late-stage diversification of bacterial natural products through biocatalysis" in Frontiers in Bioengineering and Biotechnology, 12 (2024), https://doi.org/10.3389/fbioe.2024.1351583 . .