Heterologous expression and structural characterisation of a pyrazinone natural product assembly line.
Through a number of strategies nonribosomal peptide assembly lines give rise to a metabolic diversity not possible by ribosomal synthesis. One distinction within nonribosomal assembly is that products are elaborated on an enzyme-tethered substrate, and their release is enzyme catalysed. Reductive release by NAD(P)H-dependent catalysts is one observed nonribosomal termination and release strategy. Here we probed the selectivity of a terminal reductase domain by using a full-length heterologously expressed nonribosomal peptide synthetase for the dipeptide aureusimine and were able to generate 17 new analogues. Further, we generated an X-ray structure of aureusimine terminal reductase to gain insight into the structural details associated with this enzymatic domain.
Michael G. Degroote Institute for Infectious Disease Research, McMaster University, 1200 Main St. W, Hamilton ON, L8N 3Z5, Canada.
Morgan A
MA
Wyatt
M C Y
MC
Mok
Murray
M
Junop
Nathan A
NA
Magarvey
D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D010453:Peptide Synthases / Q000737:chemistry / Q000378:metabolism; D011719:Pyrazines / Q000737:chemistry* / Q000378:metabolism*
D001688:Biological Products; D011719:Pyrazines; D010088:Oxidoreductases; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase