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.

Clavulanate-9-aldehyde 1 has been detected in Streptomyces clavuligerus and an NADPH dependent dehydrogenase capable of reducing 1 to clavulanic acid 2 has been isolated from this organism.

In the 50 years since antimicrobial agents were first introduced, bacteria have acquired a wide variety of mechanisms which have enabled them to resist the effects of these drugs. One way of overcoming this problem is to administer an antibiotic with an agent which counteracts the mechanism of resistance to that antibiotic; an example of such an approach which has already been successfully implemented is the combination of a beta-lactam antibiotic with a beta-lactamase inhibitor. This review describes antibiotic resistance mechanisms which might lend themselves to an inhibitor approach and the potential therapeutic applications of such a strategy.

The title ketocarboxylic acid [systematic name: (5R,8R,9S,10S,13R,14S,17R,20R)-3-oxo-24-norcholanic acid], C(23)H(36)O(3), forms acid-to-acid hydrogen-bonding chains [O...O = 2.620 (2) A and O-H...O = 163 (3) degrees ] in which all carboxyl groups adopt the rare anti conformation, while the ketone group does not participate in the hydrogen bonding. The occurrence and energetics of this conformation are discussed. One intermolecular C-H...O close contact exists, which plays a role in stabilizing the hydrogen-bonding arrangement.

The title ketocarboxylic acid, synthesized from the anti‐inflammatory clocortolone pivalate, crystallizes as C21H23ClO4·C6H12O, with one molecule of steroid and one of 3,3‐dimethylbutanone per asymmetric unit. The carboxyl group is highly ordered and the steroid molecules form translational carboxyl‐to‐ketone hydrogen‐bonding catemers [O...O = 2.682 (3) Å and O—H...O = 158°] that utilize the 3‐ketone group, with one chain proceeding in the [110] direction and the other in the [10] direction. One close intermolecular C—H...O=C contact is present, which involves the solvent O atom, but neither it nor the Cl atom nor the 11‐ketone group play any role in the classical hydrogen bonding.