An enzymatic cyclopentyl[b]indole formation involved in scytonemin biosynthesis.
Previous studies of the biosynthetic enzymes involved in the assembly of scytonemin (1), a cyanobacterial sunscreen, have identified beta-ketoacid 2 as an important intermediate that is produced by ThDP-dependent enzyme ScyA. We now report that ScyC, previously annotated as a hypothetical protein, catalyzes cyclization and decarboxylation of 2 to generate ketone 5. Assembly of the cyclopentyl[b]indole structure in this manner has little precedent in the chemical literature. Additional mechanistic experiments have revealed that cyclization likely precedes decarboxylation and that the latter event may provide a driving force for cyclopentane formation.
Balskus
Emily P
EP
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Walsh
Christopher T
CT
D055162:Biocatalysis; D001688:Biological Products / Q000096:biosynthesis / Q000737:chemistry; D003500:Cyclization; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D007659:Ketones / Q000378:metabolism; D050803:Leucine Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D046937:Nostoc / Q000201:enzymology; D010636:Phenols / Q000737:chemistry* / Q000378:metabolism*
D001688:Biological Products; D007211:Indoles; D007659:Ketones; D010636:Phenols; C083368:scytonemin; D050803:Leucine Dehydrogenase