Methionine Interference in Rapamycin Production Involves Repression of Demethylrapamycin Methyltransferase and S-Adenosylmethionine Synthetase

In a chemically defined medium, l-methionine decreased production of rapamycin and increased that of demethylrapamycin. Growth with l-methionine yielded cells with a lower ability to convert demethylrapamycin to rapamycin and decreased the level of S-adenosylmethionine synthetase and S-adenosylmethionine. Thus, methionine represses at least one methyltransferase of rapamycin biosynthesis and S-adenosylmethionine synthetase.