EVIDENCE OF A ROLE FOR NAD(-GLYCOHYDROLASE AND ADP-RIBOSYLTRANSFERASEIN GROWTH AND DIFFERENTIATION OF STREPTOMYCES-GRISEUS NRRL B-2682 - INHIBITION BY M-AMINOPHENYLBORONIC ACID())

m-Aminophenylboronic acid (APBA) inhibited the germination, growth and sporulation of Streptomyces griseus NRRL B-2682 in an age- and concen tration-dependent manner in submerged and solid cultures. When added t o cells or cell extracts it irreversibly inhibited NAD(+)-glycohydrola se and ADP-ribosyltransferase activity. ADP-ribosyltransferase was mor e sensitive, but inhibition was not complete, even in the presence of 10 mM APBA. The in vivo effects of the inhibitor correlated with its i n vitro effect on ADP-ribosylation and on the profile of ADP-ribosylat ed endogenous proteins. The physiological importance of ADP-ribosyltra nsferase was supported by the observation that APBA strongly inhibited the growth of a non-sporulating and NAD(+)-glycohydrolase-negative mu tant of the parental strain. The resistance of S. griseus NRRL B-2682 strains able to grow in the presence of APBA was due to permeability f actors. A comparison of the ADP-ribosylated protein profiles of S. gri seus NRRL B-2682 grown under various conditions showed similarities, b ut also specific differences. The results suggest that the ADP-ribosyl transferase of S. griseus NRRL B-2682 is an indispensable enzyme for g rowth and differentiation of the strain. It may regulate the activity of key enzymes or developmental proteins by responding to intra- and e xtracellular conditions.