2025-02-05·Journal of the American Chemical Society
Activation of Primary C–H Bonds in Oxidative Cyclizations of Tambjamines Catalyzed by Rieske Oxygenases TamC and PtTamC
Article
作者: Yu, Jian ; Oleschuk, Richard D. ; Ramachandra, Manasa ; Innis, Joshua L. M. ; Ross, Avena C. ; Howe, Graeme W. ; Sauriol, Françoise
Tambjamines are complex bipyrrole-containing natural products that possess promising bioactive properties. Although Pseudoalteromonas citrea is known to produce both cyclic tambjamine MYP1 and the linear precursor (YP1), the biosynthetic machinery used to catalyze the site-selective oxidative carbocyclization at the unactivated 1° carbon of YP1 has remained unclear. Here, we demonstrate that a three-component Rieske system consisting of an oxygenase (TamC) and two redox partner proteins is responsible for this unprecedented activity on YP1 and potentially, a non-native substrate (BE-18591). We also show that a homologous oxidase from Pseudoalteromonas tunicata (PtTamC) can function together with the partner proteins from P. citrea to process both YP1 and BE-18591. These reactions represent the first Rieske oxygenase-catalyzed activations of C-H bonds at 1° carbons, resulting in carbon-carbon bond formation. The use of TamC and PtTamC to potentially generate the new-to-nature cyclic analogue of BE-18591 suggests the enormous biocatalytic potential of these Rieske systems to facilitate late-stage oxidative cyclizations at terminal C(sp3)-H bonds.
2023-02-17·ACS chemical biology
Discovery of a Tambjamine Gene Cluster in Streptomyces Suggests Convergent Evolution in Bipyrrole Natural Product Biosynthesis
Article
作者: Pasternak, A. R. Ola ; Babulic, Jonathan L. ; Ross, Avena C. ; Grenade, Neil L. ; Chiriac, Dragos S. ; Howe, Graeme W. ; Rowland, Bronwyn E.
While bacterial natural products are a valuable source of therapeutics, the molecules produced by most biosynthetic gene clusters remain unknown. Tambjamine YP1, produced by Pseudoalteromonas tunicata, is partially derived from fatty acids siphoned from primary metabolism. A structurally similar tambjamine produced by Streptomyces, BE-18591, had not been linked to a gene cluster. Using enzymes putatively implicated in the construction of these two tambjamines, we used sequence similarity networks and gene knockout experiments to identify the biosynthetic gene cluster responsible for the production of tambjamine BE-18591 in Streptomyces albus. Despite the structural similarities between YP1 and BE-18591, the biosynthesis of the alkylamine tails of these molecules differs significantly, with the S. albus gene cluster putatively encoding a dedicated system for the construction of the fatty acid precursor to BE-18591. These different pathways in Pseudoalteromonas and Streptomyces suggest that evolutionary convergence is operative, with similar selective pressures leading to the emergence of structurally similar tambjamine natural products using different biosynthetic logic.
2007-11-01·Organic letters1区 · 化学
Total Syntheses of Tambjamines C, E, F, G, H, I and J, BE-18591, and a Related Alkaloid from the Marine Bacterium Pseudoalteromonas tunicata
1区 · 化学
Article
作者: Pinkerton, David M. ; Banwell, Martin G. ; Willis, Anthony C.
The acetate salts of tambjamines C, E, and F (2-4, respectively), as well as those of the related alkaloids BE-18591 (5) and 6, have been prepared by treatment of bipyrrole aldehyde 16 with the relevant amine in the presence of acetic acid. The 5'-bromo-analogue, 30, of compound 16 has also been prepared and used to obtain the acetate salts of tambjamines G, H, I, and J (8-11 respectively).