Biosynthesis of 5-hydroxy-4-oxo-L-norvaline in Streptomyces akiyoshiensis

The biosynthesis of 5-hydroxy-4-oxo-L-norvaline (HON) in Streptomyces akiyoshiensis has been investigated using 13C-labelled substrates. Incorporations of 13C label from sodium [1-13C]-, [2-13C]-, and [1,2-13C2]acetate indicated that HON was formed from a four-carbon compound derived from the citric acid cycle and the methyl carbon of acetate. Feeding experiments using DL-[4-13C]- and DL-[2-13C,15N]aspartate demonstrated that aspartate served as the four-carbon precursor to HON. Both enantiomers of aspartate were metabolized by S. akiyoshiensis, but the D isomer was consumed at a slower rate. The distribution of 13C label in the intracellular L-glutamic acid isolated in these feeding experiments is consistent with the operation of the citric acid cycle in S. akiyoshiensis. A biosynthetic hypothesis that involves a condensation reaction between acetyl or malonyl CoA and the β-carboxyl group of aspartate, and subsequent oxidative decarboxylation, is proposed to account for the incorporation results. An anal...