Controlling a structural branch point in ergot alkaloid biosynthesis.
The ergot alkaloids are a diverse class of fungal-derived indole alkaloid natural products with potent pharmacological activities. The biosynthetic intermediate chanoclavine-I aldehyde 1 represents a branch point in ergot biosynthesis. Ergot alkaloids festuclavine 2 and agroclavine 3 derive from alternate enzymatic pathways originating from the common biosynthetic precursor chanoclavine-I aldehyde 1. Here we show that while the Old Yellow Enzyme homologue EasA from the ergot biosynthetic gene cluster of Aspergillus fumigatus acts on chanoclavine-I aldehyde 1 to yield festuclavine 2, EasA from Neotyphodium lolii, in contrast, produces agroclavine 3. Mutational analysis suggests a mechanistic rationale for the switch in activity that controls this critical branch point of ergot alkaloid biosynthesis.
Cheng
Johnathan Z
JZ
Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Coyle
Christine M
CM
Panaccione
Daniel G
DG
O'Connor
Sarah E
SE
D001232:Aspergillus fumigatus / Q000201:enzymology; D004876:Ergot Alkaloids / Q000096:biosynthesis* / Q000737:chemistry*; D005810:Multigene Family; D009252:NADPH Dehydrogenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055328:Neotyphodium / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism
D004876:Ergot Alkaloids; D009252:NADPH Dehydrogenase