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Review
. 2015 Feb 13;290(7):3980-6.
doi: 10.1074/jbc.R114.623793. Epub 2014 Dec 4.

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

Angad P Mehta  1 , Sameh H Abdelwahed  1 , Nilkamal Mahanta  1 , Dmytro Fedoseyenko  1 , Benjamin Philmus  1 , Lisa E Cooper  1 , Yiquan Liu  1 , Isita Jhulki  1 , Steven E Ealick  2 , Tadhg P Begley  3
Affiliations
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. .

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.

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Figures

FIGURE 1.
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.
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.
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.
FIGURE 4.
Radical SAM enzymology in thiamin thiazole biosynthesis. A, tyrosine lyase (ThiH)-catalyzed reaction. B, mechanistic proposal for this reaction.
FIGURE 5.
FIGURE 5.
Radical SAM enzymology in deazaflavin biosynthesis. A, F0-synthase-catalyzed reaction. B, mechanistic proposal for F0-synthase.
FIGURE 6.
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.
FIGURE 7.
Radical SAM enzymology in menaquinone biosynthesis. Shown is the mechanistic proposal for the MqnC-catalyzed conversion of 46 to 50.
FIGURE 8.
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.
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).
See this image and copyright information in PMC

References

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