title: O-Methyltransferase is shared between the pentose phosphate and shikimate pathways and is essential for mycosporine-like amino acid biosynthesis in Anabaena variabilis ATCC 29413.
abstract: The parent core structure of mycosporine-like amino acids (MAAs) is 4-deoxygadusol, which, in cyanobacteria, is derived from conversion of the pentose phosphate pathway intermediate sedoheptulose 7-phosphate by the enzymes 2-epi-5-epivaliolone synthase (EVS) and O-methyltransferase (OMT). Yet, deletion of the EVS gene from Anabaena variabilis ATCC 29413 was shown to have little effect on MAA production, thus suggesting that its biosynthesis is not exclusive to the pentose phosphate pathway. Herein, we report how, using pathway-specific inhibitors, we demonstrated unequivocally that MAA biosynthesis occurs also via the shikimate pathway. In addition, complete in-frame gene deletion of the OMT gene from A. variabilis ATCC 29413 reveals that, although biochemically distinct, the pentose phosphate and shikimate pathways are inextricably linked to MAA biosynthesis in this cyanobacterium. Furthermore, proteomic data reveal that the shikimate pathway is the predominate route for UV-induced MAA biosynthesis.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, 150 Stamford Street, London SE1 9NH (UK).
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Pope
authors.forename: Edward
authors.initials: E
authors.lastname: Spence
authors.forename: Valentina
authors.initials: V
authors.lastname: Seralvo
authors.forename: Ranko
authors.initials: R
authors.lastname: Gacesa
authors.forename: Sibylle
authors.initials: S
authors.lastname: Heidelberger
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Weston
authors.forename: Walter C
authors.initials: WC
authors.lastname: Dunlap
authors.forename: J Malcolm
authors.initials: JM
authors.lastname: Shick
authors.forename: Paul F
authors.initials: PF
authors.lastname: Long
mesh_terms: D000596:Amino Acids / Q000096:biosynthesis*; D046870:Anabaena variabilis / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D010427:Pentose Phosphate Pathway; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012765:Shikimic Acid / Q000378:metabolism*; D014466:Ultraviolet Rays; D000097797:Glyphosate
chemical_list: D000596:Amino Acids; D001426:Bacterial Proteins; D005998:Glycine; D008780:Methyltransferases; D019761:Phosphorus-Oxygen Lyases; D012765:Shikimic Acid; D000097797:Glyphosate
keywords: microbiology; mycosporine-like amino acids; natural products; pentose phosphate pathway; shikimate pathway