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Roles of 2-oxoglutarate oxygenases and isopenicillin N synthase in β-lactam biosynthesis

Natural Product Reports, ISSN: 1460-4752, Vol: 35, Issue: 8, Page: 735-756
2018
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Article Description

Covering: up to 2017 2-Oxoglutarate (2OG) dependent oxygenases and the homologous oxidase isopenicillin N synthase (IPNS) play crucial roles in the biosynthesis of β-lactam ring containing natural products. IPNS catalyses formation of the bicyclic penicillin nucleus from a tripeptide. 2OG oxygenases catalyse reactions that diversify the chemistry of β-lactams formed by both IPNS and non-oxidative enzymes. Reactions catalysed by the 2OG oxygenases of β-lactam biosynthesis not only involve their typical hydroxylation reactions, but also desaturation, epimerisation, rearrangement, and ring-forming reactions. Some of the enzymes involved in β-lactam biosynthesis exhibit remarkable substrate and product selectivities. We review the roles of 2OG oxygenases and IPNS in β-lactam biosynthesis, highlighting opportunities for application of knowledge of their roles, structures, and mechanisms.

Bibliographic Details

Rabe, Patrick; Kamps, Jos J. A. G.; Schofield, Christopher J.; Lohans, Christopher T.

Royal Society of Chemistry (RSC)

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Chemistry

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