title: Biosynthesis of gamma-butyrolactone autoregulators that switch on secondary metabolism and morphological development in Streptomyces.
abstract: A factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) is a representative of the gamma-butyrolactone autoregulators that trigger secondary metabolism and morphogenesis in the Gram-positive, filamentous bacterial genus Streptomyces. Here, we report the A factor biosynthesis pathway in Streptomyces griseus. The monomeric AfsA, containing a tandem repeat domain of approximately 80 aa, catalyzed beta-ketoacyl transfer from 8-methyl-3-oxononanoyl-acyl carrier protein to the hydroxyl group of dihydroxyacetone phosphate (DHAP), thus producing an 8-methyl-3-oxononanoyl-DHAP ester. The fatty acid ester was nonenzymatically converted to a butenolide phosphate by intramolecular aldol condensation. The butenolide phosphate was then reduced by BprA that was encoded just downstream of afsA. The phosphate group on the resultant butanolide was finally removed by a phosphatase, resulting in formation of A factor. The 8-methyl-3-oxononanoyl-DHAP ester produced by the action of AfsA was also converted to A factor in an alternative way; the phosphate group on the ester was first removed by a phosphatase and the dephosphorylated ester was converted nonenzymatically to a butenolide, which was then reduced by a reductase different from BprA, resulting in A factor. Because introduction of afsA alone into Escherichia coli caused the host to produce a substance having A factor activity, the reductase(s) and phosphatase(s) were not specific to the A factor biosynthesis but commonly present in bacteria. AfsA is thus the key enzyme for the biosynthesis of gamma-butyrolactones.
authors.affiliation: Department of Biotechnology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Jun-ya
authors.initials: JY
authors.lastname: Kato
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Funa
authors.forename: Hidenori
authors.initials: H
authors.lastname: Watanabe
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Sueharu
authors.initials: S
authors.lastname: Horinouchi
mesh_terms: D015107:4-Butyrolactone / Q000096:biosynthesis / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D004926:Escherichia coli; D053858:Metabolic Networks and Pathways; D008660:Metabolism; D009024:Morphogenesis; D010088:Oxidoreductases / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D013302:Streptomyces / Q000166:cytology / Q000378:metabolism*
chemical_list: C108224:AfsA protein, Streptomyces griseus; D001426:Bacterial Proteins; D010088:Oxidoreductases; D010744:Phosphoric Monoester Hydrolases; D015107:4-Butyrolactone