Identification of transformation products arising from bacterial oxidation of codeine by Streptomyces griseus

Abstract

14-Hydroxycodeine and norcodeine were rigorously identified as products arising from codeine oxidation by Streptomyces griseus ATCC 10137. Both products were routinely detected in extracted culture filtrates after growth of cells in the presence of codeine for 1 week. Under these conditions, about 4 mol% of the codeine starting material was consumed, with norcodeine and 14-hydroxycodeine representing the only identifiable transformation products (molar ratio, 4:1, respectively). Extraction of a series of culture filtrates and purification of the pooled metabolites by thin-layer and high-pressure liquid chromatography led to the isolation of both biological products, the structures of which were verified by high-resolution mass spectrometry and proton nuclear magnetic resonance spectroscopy. The identities of both biological products were further confirmed by comparison of their spectral properties with those of authentic standards. This is the first report providing structural evidence for the biological formation of 14-hydroxycodeine from codeine and of codeine oxidation by S. griseus.

Cloning, nucleotide sequence determination and expression of the genes encoding cytochrome P‐450soy (soyC) and ferredoxinsoy (soyB) from Streptomyces griseus

“…The ability of Streptomyces griseus (ATCC13273) to transform a wide range of xenobiotic substrates following growth on a medium enriched with soybean flour has been well documented (Sariaslani and Rosazza, 1983;Kunz et al. 1985;Sariaslani et al.…”

Transformations of morphine alkaloids by Pseudomonas putida M10

“…However, the synthesis of 14-hydroxymorphine from morphine has not been accomplished chemically, and present syntheses of derivatives hydroxylated at C-14 rely on thebaine, which is a minor component of opium poppy alkaloids, as a starting material. This has been attributed to the saturated and therefore unreactive nature of the carbon at C-14 in morphine and codeine, whereas in thebaine this carbon is olefinic and readily undergoes hydroxylation (12). Biologically catalyzed reactions would, therefore, greatly facilitate these syntheses since morphine and codeine could be utilized as starting materials.…”

“…Biologically catalyzed reactions would, therefore, greatly facilitate these syntheses since morphine and codeine could be utilized as starting materials. The oxidation of codeine to 14␤-hydroxycodeine by S. griseus (12) is the only reported transformation of this type by a bacterium in which the product has been fully identified by 1 H NMR and mass spectral analyses. Such a biotransformation with morphine as substrate has never been fully established.…”

“…A few bacterial transformations of morphine alkaloids have also been reported: for example, transformation of morphine to 14␤-hydroxymorphine in low yields by an Arthrobacter sp. (13) and transformation of codeine to 14␤-hydroxycodeine and N-norcodeine by Streptomyces griseus (12). Early attempts to prepare novel alkaloid analogs using microorganisms were limited to exploring the range of transformations available, relying on fortuitous side reactions due to enzymes with broad substrate specificities.…”

Microbial degradation of the morphine alkaloids. Purification and characterization of morphine dehydrogenase from Pseudomonas putida M10

“…The morphine alkaloids have attracted considerable attention owing to their analgaesic properties and, consequently, much effort in the past has been directed at the production of new morphine alkaloids by micro-organisms (lizuka et al, 1960Yamada et al, 1962Yamada et al, , 1963Liras & Umbreit, 1975;Gibson et al, 1984;Kunz et al, 1985;Spassov et al, 1986). It is therefore perhaps surprising that there have been few reports on the utilization by micro-organisms of these alkaloid compounds as sole carbon and energy sources.…”