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Labelling experiments are described that identify three new compounds, N*-(2-carboxyethyl)arginine, 5-guanidino-(2-oxoazetidin-l-yl)pentanoic acid, and 3-hydroxy-5-guanidino-2-( 2-oxoazetidin-I -yl)pentanoic acid as biosynthetic precursors of proclavaminic acid and hence clavulanic acid in Streptom yces clavuligerus ATCC 27064 and a new amidino hydrolase, which hydrolyses 3-hydroxy-5-guanidino-2-(2-oxoazetidin-l -yl)pentanoic acid to proclavaminic acid has been characterised. As part of our goal to elucidate the biosynthesis of clavulanicAlso we reported4 on the production of two new arginine acid 11** we demonstrated3 that arginine 2 and not ornithine is derivatives 3 and 4 by the mutant S . clavuligerus dclH 65 which the amino acid that is processed into the biosynthetic pathway.is blocked in clavulanic acid biosynthesis. In addition, sequencing of the DNA of the clavulanic acid gene cluster identified an open reading frame, which showed homology to arginaseaS From these data we can postulate a number of possible biosynthetic sequences prior to prOClaVaminiC acid 5 which are shown in Scheme 1.

lncu bation of (2S,3S)-5-guanidino[2,3-2H2]-2-(2'-oxoazetidin-l '-yl)pentanoic acid and (2S,3R)-5-guanidino-[3-2H1]-2-(2'-oxoazetidin-1 '-y1)pentanoic acid with clavaminic acid synthase resulted in highly stereospecific hydroxylation at C-3, with removal of the pro-R hydrogen or deuterium, respectively.