Structural highlights
Function
SALL_SALTO Involved in the biosynthesis of the proteosome inhibitor salinosporamide A (SalA). Catalyzes the halogenation of S-adenosyl-L-methionine (SAM) with chloride to generate 5'-chloro-5'-deoxyadenosine (5'-CIDA) and L-methionine. It can also use bromide and iodide, producing halogenated 5'-deoxyadenosine (5'-XDA) and L-methionine, however no halogenase activity is detected in the presence of fluoride.[1]
Publication Abstract from PubMed
A tandem enzymatic strategy to enhance the scope of C-alkylation of small molecules via the in situ formation of S-adenosyl methionine (SAM) cofactor analogues is described. A solvent-exposed channel present in the SAM-forming enzyme SalL tolerates 5'-chloro-5'-deoxyadenosine (ClDA) analogues modified at the 2-position of the adenine nucleobase. Coupling SalL-catalyzed cofactor production with C-(m)ethyl transfer to coumarin substrates catalyzed by the methyltransferase (MTase) NovO forms C-(m)ethylated coumarins in superior yield and greater substrate scope relative to that obtained using cofactors lacking nucleobase modifications. Establishing the molecular determinants that influence C-alkylation provides the basis to develop a late-stage enzymatic platform for the preparation of high value small molecules.
S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation.,McKean IJW, Sadler JC, Cuetos A, Frese A, Humphreys LD, Grogan G, Hoskisson PA, Burley GA Angew Chem Int Ed Engl. 2019 Dec 2;58(49):17583-17588. doi:, 10.1002/anie.201908681. Epub 2019 Oct 21. PMID:31573135[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Eustaquio AS, Pojer F, Noel JP, Moore BS. Discovery and characterization of a marine bacterial SAM-dependent chlorinase. Nat Chem Biol. 2008 Jan;4(1):69-74. Epub 2007 Dec 2. PMID:18059261 doi:http://dx.doi.org/10.1038/nchembio.2007.56
- ↑ McKean IJW, Sadler JC, Cuetos A, Frese A, Humphreys LD, Grogan G, Hoskisson PA, Burley GA. S-Adenosyl Methionine Cofactor Modifications Enhance the Biocatalytic Repertoire of Small Molecule C-Alkylation. Angew Chem Int Ed Engl. 2019 Dec 2;58(49):17583-17588. PMID:31573135 doi:10.1002/anie.201908681
