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Porphyrin Overproduction by Pseudomonas denitrificans: Essentiality of Betaine and Stimulation by Ethionine

^a Fermentation Research Department, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065

ABSTRACT

Ethionine supplementation of a defined medium for growth of Pseudomonas denitrificans inhibited vitamin B₁₂ overproduction and led to the elaboration of a red pigment. The pigment was shown to be coproporphyrin III. Inhibition by ethionine of cobalamin synthesis is probably due to interference of methylation of the corrin nucleus by methionine. Accumulation of coproporphyrin III is thought to result from interference by ethionine with the activity of methionine in the coproporphyrinogenase reaction; this would inhibit formation of heme, the feedback inhibitor and corepressor of -aminolevulinate synthetase, thus allowing unregulated synthesis of coproporphyrinogen III and its degradation product, coproporphyrin III. Betaine, known to be required for vitamin B12 overproduction, was found to be an essential requirement for porphyrin overproduction in the presence of ethionine. Low-level production of porphyrin, which occurs in the absence of ethionine, also required betaine supplementation. Betaine is thus required for overproduction of both corrins and porphyrins in P. denitrificans.

¹ Present address: Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Mass. 02139.