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Review
. 2009 Aug 26;7(3):401-34.
doi: 10.3390/md7030401.

Marine-derived metabolites of S-adenosylmethionine as templates for new anti-infectives

Janice R Sufrin  1 , Steven Finckbeiner, Colin M Oliver
Affiliations
Review

Marine-derived metabolites of S-adenosylmethionine as templates for new anti-infectives

Janice R Sufrin et al. Mar Drugs. .

Abstract

S-Adenosylmethionine (AdoMet) is a key biochemical co-factor whose proximate metabolites include methylated macromolecules (e.g., nucleic acids, proteins, phospholipids), methylated small molecules (e.g., sterols, biogenic amines), polyamines (e.g., spermidine, spermine), ethylene, and N-acyl-homoserine lactones. Marine organisms produce numerous AdoMet metabolites whose novel structures can be regarded as lead compounds for anti-infective drug design.

Keywords: adenosylmethionine; ethylene; polyamines; quorum sensing; radical SAM.

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Figures

Figure 1
Figure 1
S-Adenosylmethionine biosynthesis. Structural components of AdoMet are color coded.
Figure 2
Figure 2
Structures of marine-derived, precursor-validated AdoMet metabolites. AdoMet-derived methyl groups are shown in green.
Figure 3
Figure 3
Polyamine Biosynthesis. Structural components derived from AdoMet are color coded. SAMDC, S-adenosylmethionine decarboxylase; ODC, ornithine decarboxylase; SpdS, spermidine synthase; SpmS, spermine synthase.
Figure 4
Figure 4
Structures of marine-derived polyamine conjugates. AdoMet-derived aminopropyl (blue) and methyl (green) groups are depicted.
Figure 5
Figure 5
Biological methylation pathways. AdoMet-derived methyl groups are shown in green. AdoHcy, S-adenosylhomocysteine; PCMT, protein carboxymethyltransferase; PRMT, protein arginine methyltransferase; HMT, histone methyltransferase; DNMT, DNA methyltransferase; GNMT, guanosine N-methyltransferase; NOMT, nucleoside O-methyltransferase; PLMT, phospholipid methyltransferase; SMT, sterol methyltransferase; COMT, catechol O-methyltransferase; PNMT, phenylethanolamine N-methyltransferase.
Figure 6
Figure 6
Structures of marine-derived methylated purines. AdoMet-derived methyl groups are shown in green.
Figure 6
Figure 6
Structures of marine-derived methylated purines. AdoMet-derived methyl groups are shown in green.
Figure 7
Figure 7
Cortistatins (CS). AdoMet-derived methyl groups are shown in green.
Figure 8
Figure 8
Ethylene biosynthesis. Structural components derived from AdoMet are color coded. ACC, 1-aminocyclopropane-1-carboxylate; ACCS, 1-aminocyclopropane-1-carboxylate synthase; ACCO, 1-aminocyclopropane-1-carboxylate oxidase.
Figure 9
Figure 9
AdoMet-dependent halogenation pathways. A halogen is enzymatically transferred to AdoMet, releasing methionine to generate 5’-halo-5’-deoxyadenosine. SalL, AdoMet-dependent chlorinase; PNP, purine nucleoside phosphorylase; PKS/NRPS, polyketide synthase/nonribosomal peptide synthetase.
Figure 10
Figure 10
. Radical SAM pathways [11,127,128]. AdoMet is utilized as a protein cofactor or catalyst in radical SAM reactions. These proteins contain an embedded iron-sulfur cluster that binds AdoMet, releases methionine and generates a deoxyadenosine (DOA) radical. The DOA radical transfers an electron to the enzyme substrate to generate a substrate radical. Structural components derived from AdoMet are color coded.
Figure 11
Figure 11
N-Acylhomoserine lactone biosynthesis. Structural components derived from AdoMet are color coded. LasI, AHL synthase. OdDHL, N-3-oxo-dodecanoyl-l-homoserine lactone.
Figure 12
Figure 12
Acylhomoserine lactones from marine bacteria genus Vibrio. Structural components derived from AdoMet are color coded. HBHL, N-3-hydroxy-butanoyl-l-homoserine lactone; OHHL, N-3-oxo-hexanoyl-l-homoserine lactone; OHL, N-octanoyl-l-homoserine lactone.
Figure 13
Figure 13
AHLs produced by marine bacteria genus Mesorhizobium. Structural components derived from AdoMet are color coded.
Figure 14
Figure 14
AHLs produced by marine bacteria genus Roseobacter. Asterisks indicate double bonds whose location and cis-, trans-orientations are unknown. Structural components derived from AdoMet are color coded.
Figure 15
Figure 15
AI-2 biosynthesis. The byproduct of biological methylation pathways, AdoHcy, is enzymatically metabolized through two steps to yield DPD (4S-4,5-dihydroxypentane-2,3-dione), which is generated from the ribose ring of AdoMet. DPD spontaneously cyclizes and binds boric acid to form autoinducer 2 (AI-2). Structural components derived from AdoMet are color coded. MT, methyltransferase; AHN, adenosylhomocysteine nucleosidase; RHcy, ribosylhomocysteine; LuxS, S-ribosylhomocysteine lyase.
Figure 16
Figure 16
The P. aeruginosa QS signal, N-3-oxo-dodecanoyl-l-homoserine lactone, OdDHL, undergoes spontaneous degradation to form a tetramic acid [149].
Figure 17
Figure 17
TON-1 (RK-682, 3-alkanoyl-5-hydroxymethyl tetronic acid) can serve as a retro-template for related AHL and tetramic acid structures. AHL-16, TAM-2 and TON-2 are putative structures. Structural components derived from AdoMet are color coded.
Figure 18
Figure 18
Quorum sensing antagonists. Halogenated furanones of D. pulchra interfere with AHL-mediated QS pathways of Serratia liquefaciens. Structural components derived from AdoMet are color coded. BHL, N-butanoyl-l-homoserine lactone; HHL, N-hexanoyl-l-homoserine lactone.
Figure 19
Figure 19
Unusual marine-derived metabolites of AdoMet (UM). Structural components derived from AdoMet are color coded.
See this image and copyright information in PMC

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