Radical S-adenosylmethionine (SAM) enzymes in cofactor biosynthesis: a treasure trove of complex organic radical rearrangement reactions - PubMed (original) (raw)

Review

Radical S-adenosylmethionine (SAM) enzymes in cofactor biosynthesis: a treasure trove of complex organic radical rearrangement reactions

Angad P Mehta et al. J Biol Chem. 2015.

Abstract

In this minireview, we describe the radical S-adenosylmethionine enzymes involved in the biosynthesis of thiamin, menaquinone, molybdopterin, coenzyme F420, and heme. Our focus is on the remarkably complex organic rearrangements involved, many of which have no precedent in organic or biological chemistry.

Keywords: Biosynthesis; Deazaflavin; Enzyme Mechanism; Heme; Menaquinone; Molybdopterin; Rearrangement; S-Adenosylmethionine (SAM); Thiamin; radical.

PubMed Disclaimer

Figures

FIGURE 1.

Cofactor biosynthetic pathways make extensive use of radical SAM enzymology. The structures of the five cofactors described in this minireview are shown.

FIGURE 2.

Examples of the major radical reactions found in organic chemistry. A, hydrogen atom abstraction, e.g. 6 to 10 and 14 to 15. B, addition to double bonds, e.g. 15 to 16. C–E, β-bond scission reactions, e.g. 10 to 11, 16 to 17, 17 to 18+19, 19 to 21, 22 to 23, 24 to 25, and 25 to 26. All enzymatic examples are taken from Fig. 3.

FIGURE 3.

Radical SAM enzymology in thiamin pyrimidine biosynthesis. A, results of a comprehensive labeling study to determine the fate of all of the atoms of AIR (6) during the formation of the HMP-P (8). B, mechanistic proposal for the formation of HMP-P (8).

FIGURE 4.

Radical SAM enzymology in thiamin thiazole biosynthesis. A, tyrosine lyase (ThiH)-catalyzed reaction. B, mechanistic proposal for this reaction.

FIGURE 5.

Radical SAM enzymology in deazaflavin biosynthesis. A, F0-synthase-catalyzed reaction. B, mechanistic proposal for F0-synthase.

FIGURE 6.

Radical SAM enzymology in menaquinone biosynthesis. A, reaction catalyzed by aminofutalosine synthase (MqnE). B, mechanistic proposal for the MqnE-catalyzed reaction.

FIGURE 7.

Radical SAM enzymology in menaquinone biosynthesis. Shown is the mechanistic proposal for the MqnC-catalyzed conversion of 46 to 50.

FIGURE 8.

Radical SAM enzymology in molybdopterin biosynthesis. A, MoaA-catalyzed reaction. B, mechanistic proposal for the conversion of GTP (51) to the pterin (52).

FIGURE 9.

Radical SAM enzymology in heme biosynthesis. Shown is the mechanistic proposal for the coproporphyrinogen III oxidase (HemN)-catalyzed formation of protoporphyrinogen IX (63).

Cited by

New Insight into the Mechanism of Anaerobic Heme Degradation.
Mathew LG, Beattie NR, Pritchett C, Lanzilotta WN. Mathew LG, et al. Biochemistry. 2019 Nov 19;58(46):4641-4654. doi: 10.1021/acs.biochem.9b00841. Epub 2019 Nov 7. Biochemistry. 2019. PMID: 31652058 Free PMC article.
Radical SAM Enzymes Involved in Tetrapyrrole Biosynthesis and Insertion.
Layer G, Jahn M, Moser J, Jahn D. Layer G, et al. ACS Bio Med Chem Au. 2022 Feb 16;2(3):196-204. doi: 10.1021/acsbiomedchemau.1c00061. eCollection 2022 Jun 15. ACS Bio Med Chem Au. 2022. PMID: 37101575 Free PMC article. Review.
Recent Advances in Enzymatic Complexity Generation: Cyclization Reactions.
Walsh CT, Tang Y. Walsh CT, et al. Biochemistry. 2018 Jun 5;57(22):3087-3104. doi: 10.1021/acs.biochem.7b01161. Epub 2017 Dec 20. Biochemistry. 2018. PMID: 29236467 Free PMC article. Review.
RaS-RiPPs in Streptococci and the Human Microbiome.
Clark KA, Bushin LB, Seyedsayamdost MR. Clark KA, et al. ACS Bio Med Chem Au. 2022 Aug 17;2(4):328-339. doi: 10.1021/acsbiomedchemau.2c00004. Epub 2022 Mar 21. ACS Bio Med Chem Au. 2022. PMID: 35996476 Free PMC article. Review.
β-NAD as a building block in natural product biosynthesis.
Barra L, Awakawa T, Shirai K, Hu Z, Bashiri G, Abe I. Barra L, et al. Nature. 2021 Dec;600(7890):754-758. doi: 10.1038/s41586-021-04214-7. Epub 2021 Dec 8. Nature. 2021. PMID: 34880494

References

1. Broderick J. B., Duffus B. R., Duschene K. S., Shepard E. M. (2014) Radical S-adenosylmethionine enzymes. Chem. Rev. 114, 4229–4317 - PMC - PubMed
1. Sofia H. J., Chen G., Hetzler B. G., Reyes-Spindola J. F., Miller N. E. (2001) Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods. Nucleic Acids Res. 29, 1097–1106 - PMC - PubMed
1. Atkinson J. K., Ingold K. U. (1993) Cytochrome P450 hydroxylation of hydrocarbons: variation in the rate of oxygen rebound using cyclopropyl radical clocks including two new ultrafast probes. Biochemistry 32, 9209–9214 - PubMed
1. Chatterjee A., Li Y., Zhang Y., Grove T. L., Lee M., Krebs C., Booker S. J., Begley T. P., Ealick S. E. (2008) Reconstitution of ThiC in thiamin pyrimidine biosynthesis expands the radical SAM superfamily. Nat. Chem. Biol. 4, 758–765 - PMC - PubMed
1. Chatterjee A., Hazra A. B., Abdelwahed S., Hilmey D. G., Begley T. P. (2010) A radical dance in thiamin biosynthesis: mechanistic analysis of the bacterial hydroxymethylpyrimidine phosphate synthase. Angew. Chem. Int. Ed. Engl. 49, 8653–8656 - PMC - PubMed

Radical S-adenosylmethionine (SAM) enzymes in cofactor biosynthesis: a treasure trove of complex organic radical rearrangement reactions - PubMed (original) (raw)