title: Biosynthesis of the nargenicin A1 pyrrole moiety from Nocardia sp. CS682.
abstract: A number of structurally diverse natural products harboring pyrrole moieties possess a wide range of biological activities. Studies on biosynthesis of pyrrole ring have shown that pyrrole moieties are derived from L-proline. Nargenicin A(1), a saturated alicyclic polyketide from Nocardia sp. CS682, is a pyrrole-2-carboxylate ester of nodusmicin. We cloned and identified a set of four genes from Nocardia sp. CS682 that show sequence similarity to the respective genes involved in the biosynthesis of the pyrrole moieties of pyoluteorin in Pseudomonas fluorescens, clorobiocin in Streptomyces roseochromogenes subsp. Oscitans, coumermycin A(1) in Streptomyces rishiriensis, one of the pyrrole rings of undecylprodigiosin in Streptomyces coelicolor, and leupyrrins in Sorangium cellulosum. These genes were designated as ngnN4, ngnN5, ngnN3, and ngnN2. In this study, we presented the evidences that the pyrrole moiety of nargenicin A(1) was also derived from L-proline by the coordinated action of three proteins, NgnN4 (proline adenyltransferase), NgnN5 (proline carrier protein), and NgnN3 (flavine-dependent acyl-coenzyme A dehydrogenases). Biosynthesis of pyrrole moiety in nargenicin A(1) is initiated by NgnN4 that catalyzes ATP-dependent activation of L-proline into L-prolyl-AMP, and the latter is transferred to NgnN5 to create prolyl-S-peptidyl carrier protein (PCP). Later, NgnN3 catalyzes the two-step oxidation of prolyl-S-PCP into pyrrole-2-carboxylate. Thus, this study presents another example of a pyrrole moiety biosynthetic pathway that uses a set of three genes to convert L-proline into pyrrole-2-carboxylic acid moiety.
authors.affiliation: Institute of Biomolecule Reconstruction, Sun Moon University, 100 Kalsan-ri, Tangjeonmyun, Asansi, Chungnam, 336-708, South Korea.
authors.forename: Sushila
authors.initials: S
authors.lastname: Maharjan
authors.forename: Niraj
authors.initials: N
authors.lastname: Aryal
authors.forename: Saurabh
authors.initials: S
authors.lastname: Bhattarai
authors.forename: Dinesh
authors.initials: D
authors.lastname: Koju
authors.forename: Janardan
authors.initials: J
authors.lastname: Lamichhane
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D005798:Genes, Bacterial; D007783:Lactones / Q000378:metabolism; D009615:Nocardia / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000378:metabolism; D011758:Pyrroles / Q000378:metabolism*; D014166:Transferases / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D007783:Lactones; D011758:Pyrroles; C034624:nargenicin A1; D000255:Adenosine Triphosphate; D011392:Proline; D042964:Acyl-CoA Dehydrogenase; D014166:Transferases