Roles of the Dimethylamino Group and Macrodiolide Ring of Pamamycin-607 in Its Aerial Mycelium-inducing Activity

Abstract

Four pamamyciu..(j07-degraded products-desdimethylaminopamamycin-607, a macrodiolide ring-opened compound, and two constitutent hydroxy acids-were prepared, and their aerial mycelium-inducing activity was measured. The hydroxy acid L part with a dimethyl amino group was the principal component responsible for activity. The macrodiolide ring itself was dispensable, but only hydroxy acid L showed very weak activity.

Nitrogen Incorporation in the Biosynthetic Pathway of the Nitrogen-containing Polyketide, Pamamycin in Streptomyces alboniger

“…This regulatory mechanism of pamamycin production is reasonable because introduction of a nitrogen atom has been reported to be essential for aerial mycelium-inducing activity [6,10].…”

“…These results showed that 7 was incorporated into 1. 13 C-labeled 7 with 5 also increased intensities of isotope peaks of de-N-methylpamamycin (6) in cultured materials (data not shown).…”

“…The extract contained hydroxy acid L (4) with MWs 413, 427 and 441, and hydroxy acid S (5) with MWs 230, 244 and 258. Proportion of hydroxy acid L with MW 413 (4; R 1 , R 2 , R 3 ϭCH 3 ), which is component of pamamycin-607 [6], was 20% of total hydroxy acid L, and that of hydroxy acid S with MW 230 (5; R 4 ϭCH 3 , R 5 ϭH) was 15% of total hydroxy acid S. This mixture was used for bioconversion of 4 and 5 to 1.…”

“…It is still unknown when the nitrogen atom is introduced into the carbon skeleton. We are interested in investigating nitrogen incorporation during biosynthesis of pamamycin because the dimethylamino group of pamamycin-607 is indispensable for aerial mycelium-inducing activity [6] and nitrogen-containing polyketides are rare.…”

“…C-NMR spectra were obtained with a JEOL JNM A-600 spectrometer at 150 MHz in acetone-d 6 with an equimolar amount of CF 3 COOD. GC-MS analyses were performed with a JEOL SX-102 A spectrometer.…”