title: The genetic and molecular basis for sunscreen biosynthesis in cyanobacteria.
abstract: Ultraviolet UV-A and UV-B radiation is harmful to living systems, causing damage to biological macromolecules. An important strategy for dealing with UV exposure is the biosynthesis of small-molecule sunscreens. Among such metabolites, the mycosporine and mycosporine-like amino acids (MAAs) are remarkable for their wide phylogenetic distribution and their unique chemical structures. Here, we report the identification of a MAA biosynthetic gene cluster in a cyanobacterium and the discovery of analogous pathways in other sequenced organisms. We have expressed the cluster in a heterologous bacterial host and characterized all four biosynthetic enzymes in vitro. In addition to clarifying the origin of the MAAs, these efforts have revealed two unprecedented enzymatic strategies for imine formation.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Emily P
authors.initials: EP
authors.lastname: Balskus
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Walsh
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D046870:Anabaena variabilis / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D055162:Biocatalysis; D003001:Cloning, Molecular; D003511:Cyclohexanols; D003514:Cyclohexylamines / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D005998:Glycine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D007097:Imines / Q000378:metabolism; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D046937:Nostoc / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D016366:Open Reading Frames; D013473:Sunscreening Agents / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D001426:Bacterial Proteins; D003511:Cyclohexanols; D003514:Cyclohexylamines; D007097:Imines; D013473:Sunscreening Agents; C463482:mycosporine-2-glycine; D000255:Adenosine Triphosphate; C494891:shinorine; D008780:Methyltransferases; D008025:Ligases; D005998:Glycine
references.citation: Biol Rev Camb Philos Soc. 1999 Aug;74(3):311-45
references.pmid: 10466253
references.citation: Genomics. 2010 Feb;95(2):120-8
references.pmid: 19879348
references.citation: Chembiochem. 2007 Jan 22;8(2):239-48
references.pmid: 17195255
references.citation: Chem Biol. 1999 Aug;6(8):493-505
references.pmid: 10421756
references.citation: Comp Biochem Physiol B Biochem Mol Biol. 2004 Dec;139(4):721-30
references.pmid: 15581804
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2533-7
references.pmid: 18268342
references.citation: Nat Prod Rep. 1998 Apr;15(2):159-72
references.pmid: 9586224
references.citation: Photochem Photobiol. 2008 Nov-Dec;84(6):1500-5
references.pmid: 18557824
references.citation: Nature. 1966 Oct 8;212(5058):163-4
references.pmid: 5972212
references.citation: FEMS Microbiol Lett. 2007 Apr;269(1):1-10
references.pmid: 17286572
references.citation: Protein Sci. 1997 Dec;6(12):2639-43
references.pmid: 9416615
references.citation: Biochemistry. 1989 Sep 19;28(19):7555-60
references.pmid: 2514789
references.citation: Chem Rev. 2006 Aug;106(8):3468-96
references.pmid: 16895337
references.citation: J Nat Prod. 2007 Aug;70(8):1384-91
references.pmid: 17661520
references.citation: J Dermatol Sci. 2009 Sep;55(3):161-9
references.pmid: 19586754
references.citation: Annu Rev Physiol. 2002;64:223-62
references.pmid: 11826269