Biosynthesis of nodulisporic acid A: precursor studies.
Nodulisporic acid A (NAA) is an indole-diterpene natural product produced by an indeterminate species of the endophytic fungus Nodulisporium. NAA (Figure 1) is structurally related to the paspaline class of fungal metabolites. The biosynthetic origin proposed for these alkaloids involves the acetate/mevalonic acid pathway leading to geranylgeranyl pyrophosphate (GGPP). GGPP is then proposed to condense with tryptophan to form the basic indole-diterpene core. A washed cell procedure was devised to incorporate labeled precursors into NAA by a mutant Nodulisporium culture designated MF6244. Incorporation of 2-(13)C-acetate and 2-(13)C-mevalonolactone into NAA was found to occur in the classical mevalonic acid pattern. In addition to the four mevalonic acid units that form the eastern side of the molecule, three additional isoprenylations occur to form the western and southern regions of NAA. Contrary to published reports on related compounds, incubations of Nodulisporium MF6244 with (14)C- and (13)C-tryptophan showed no incorporation of label into NAA. However, high levels of incorporation into NAA were obtained with known tryptophan precursors (14)C-, (13)C-, and (15)N-anthranilic acid and (14)C- and (13)C-ribose. A novel pathway for the biosynthesis of NAA is presented.
Byrne
Kevin M
KM
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065-0900, USA. kevin_byrne@merck.com
Smith
Scott K
SK
Ondeyka
John G
JG
D000085:Acetates / Q000378:metabolism; D001203:Ascomycota / Q000378:metabolism*; D002250:Carbon Radioisotopes; D007211:Indoles / Q000378:metabolism*; D007553:Isotope Labeling; D008798:Mevalonic Acid / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D012266:Ribose / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000378:metabolism
D000085:Acetates; D002250:Carbon Radioisotopes; D007211:Indoles; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; C110703:nodulisporic acid A; D012266:Ribose; D014364:Tryptophan; D008798:Mevalonic Acid