Biocatalytic role of cytochrome P450s to produce antibiotics: A review |
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Authors: | Anup Adhikari Sajan Shakya Shreesti Shrestha Dipa Aryal Kavi Prasad Timalsina Dipesh Dhakal Yogan Khatri Niranjan Parajuli |
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Affiliation: | 1. Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu, Nepal;2. Department of Biotechnology, National College, Tribhuvan University, Kathmandu, Nepal;3. Department of Medicinal Chemistry, Center for Natural Products, Drug Discovery and Development, University of Florida, Gainesville, Florida, USA;4. Cayman Chemical, Ann Arbor, Michigan, USA |
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Abstract: | Cytochrome P450s belong to a family of heme-binding monooxygenases, which catalyze regio- and stereospecific functionalisation of C–H, C–C, and C–N bonds, including heteroatom oxidation, oxidative C–C bond cleavages, and nitrene transfer. P450s are considered useful biocatalysts for the production of pharmaceutical products, fine chemicals, and bioremediating agents. Despite having tremendous biotechnological potential, being heme-monooxygenases, P450s require either autologous or heterologous redox partner(s) to perform chemical transformations. Randomly distributed P450s throughout a bacterial genome and devoid of particular redox partners in natural products biosynthetic gene clusters (BGCs) showed an extra challenge to reveal their pharmaceutical potential. However, continuous efforts have been made to understand their involvement in antibiotic biosynthesis and their modification, and this review focused on such BGCs. Here, particularly, we have discussed the role of P450s involved in the production of macrolides and aminocoumarin antibiotics, nonribosomal peptide (NRPSs) antibiotics, ribosomally synthesized and post-translationally modified peptide (RiPPs) antibiotics, and others. Several reactions catalyzed by P450s, as well as the role of their redox partners involved in the BGCs of various antibiotics and their derivatives, have been primarily addressed in this review, which would be useful in further exploration of P450s for the biosynthesis of new therapeutics. |
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Keywords: | antibiotics biosynthesis bacterial cytochrome P450 microbial natural products Streptomyces |
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