James Staunton made outstanding contributions to our knowledge of the biosynthesis of natural products. His early work with Alan Battersby on the alkaloids led to independent research from 1970 on polyketides, a family including many important antibiotics. Details of the biosynthesis of citrinin, sclerin, canescin and terrein were elucidated mainly using stable isotopes, and James devised novel techniques, for example the NMR beta-shift method for deuterium detection. He demonstrated by biomimetic syntheses how the cyclisation of polyketones to aromatic polyketides is controlled; his conclusions have been shown to hold good for natural products ranging from naphthalenes to tetracyclines. James recognised early the importance of combining chemical and biological approaches for research on aliphatic polyketides leading to the black box of polyketide biosynthesis being opened. James pioneered the use of electrospray mass spectrometry for the detection of intermediates bound to enzymes involved polyketide biosynthesis. His research on polyketide synthases (PKS) has transformed knowledge of these enzymes. James was widely regarded as a leader in his field.