[Objective] To study the relationship between S-adenosylmethionine synthetase (SAMs) activity and the biosynthesis of epothilone. [Methods] We analyzed the relationship between the activities of SAMs and the yields of epothilone by the addition of inhibitor and accelerator. [Results] SAMs showed high activities in the period of the biosynthesis of epothilone. SAMs activities and the yields of epothilones both reduced with the indole-3-acetic acid addition and increased with the sodium p-toluenesulfonate addition. The SAMs activities were positive correlated with the yields of epothilone when the inhibitor or accelerator was added. [Conclusion] SAMs play an important role in the biosynthesis of epothilone in Sorangium cellulosums.