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Effect of nipecotic acid. (A) Under normal conditions for rapamycin fermentation, rapamycin was the primary product. (B) With the addition of (±)-nipecotic acid to the fermentation, prolyl-rapamycin became the major product. (C) Adding l-pipecolic acid to the production medium restored rapamycin production. The retention times were as follows: prolyl-rapamycin, 22.9 min; rapamycin, 24.1 min.
