The structure and absolute configuration of pentalenolactone (PA 132)

Arenaemycin (pentalenolactone): a specific inhibitor of glycolysis

“…These observations suggested that arenaemycin interferes with a glycolytic reaction which is not involved in gluconeogenesis [2]. A recent survey (W. Keller-Schierlein, personal communication) showed by comparison of the chemical data [2-41 that arenaemycin E is identical with pentalenolactone, an antibiotic isolated from the fermented broth of different Streptomyces species in the course of screening programs for antimeta- bolites with antitumor activity [3,4] . The structure and absolute configuration was determined [4] and is shown in fig.1.…”

“…A recent survey (W. Keller-Schierlein, personal communication) showed by comparison of the chemical data [2-41 that arenaemycin E is identical with pentalenolactone, an antibiotic isolated from the fermented broth of different Streptomyces species in the course of screening programs for antimeta- bolites with antitumor activity [3,4] . The structure and absolute configuration was determined [4] and is shown in fig.1. The data presented here show that arenaemycin E/pentalenolactone is a potent and selective inhibitor of glyceraldehyde3-phosphate dehydrogenase (EC 1.2.1.12).…”

Nature as organic chemist

“…19,20 The project got off to a very slow start, when for more than a year all of our attempts to incorporate simple acetate or mevalonate precursors into pentalenolactone were fruitless. Eventually, I had the idea to feed the Streptomyces culture uniformly labeled [ 13 C 6 ]glucose, which I assumed would act as an in vivo precursor of [1,2-13 C 2 ]acetyl-CoA.…”

“…Within the first 6 months our groups achieved the first in vitro enzyme-catalyzed synthesis of 6-deoxyerythronolide B (19) from propionyl-CoA, methylmalonyl-CoA, and NADPH using a mixture of DEBS1, 2, and 3 expressed from S. coelicolor (Figure 14a). 108 We also described the enzymatic formation of the triketide lactone (20) by recombinant DEBS1+TE alone, a chimeric protein carrying the natural DEBS thioesterase (TE) domain from module 6 fused to the C-terminus of module 2 in order to facilitate release of the triketide and permit multiple catalytic turnovers (Figure 14b). Over the following years, Chaitan and his coworkers developed numerous powerful methods for the production and isolation of active individual PKS modules and individual recombinant PKS domains, first from S. coelicolor and then from E. coli.…”

Product-Mediated Regulation of Pentalenolactone Biosynthesis in Streptomyces Species by the MarR/SlyA Family Activators PenR and PntR

“…Pentalenolactone (Fig. 1) is a widely occurring sesquiterpene metabolite that has been isolated from more than 30 species of Streptomyces (12)(13)(14)(15). Its antibiotic action against bacteria, fungi, and protozoa is due to the presence of an electrophilic epoxylactone moiety that alkylates the active-site cysteine of the target glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (16)(17)(18).…”