Isolation, structure and biological activities of platensimycin B4 from Streptomyces platensis

Abstract

Platensimycin and platencin are inhibitors of FabF and FabF/H bacterial fatty acid synthesis enzymes, respectively. Discovery of natural congeners provides one of the ways to understand the relationship of chemical structure and biological function. Efforts to discover the natural analogs of platensimycin by chemical screening led to the isolation of platensimycin B 4 , a glucoside congener of platensimycin. This analog showed significantly attenuated activity and critically defined the limited binding space around the aromatic ring and established the importance of the free phenolic and carboxyl group for the activity.

A comprehensive review of glycosylated bacterial natural products

“…Diterpenes are comprised of four isoprene units and 16 glycosylated diterpenoids have been reported as metabolites of Strepomyces and Nocardia including the phenalinolactones, 1259 lucensimycins, 1260 brasillicardins, 1261,1262 platensimycins, 1263 and platencins. 1264,1265 Phenalinolactones, C-4 glycosides of a methylated α-L-amicetose ( 97 ) (Fig.…”

“…58) and it is important to point out that some confusion exists in the literature regarding the structure of pseudodisaccharide II . 1131 Platensimycin B 4 and its methyl ester 1263 and platencins A9, A10 and A12–A15 1264,1265 are the known glycosylated derivatives of the platensimycins and platencins. Members of this class were found to be potent inhibitors of mammalian and bacterial fatty acid synthases with potential relevance for the treatment of metabolic disease and bacterial infections.…”

Platensimycin and platencin: Inspirations for chemistry, biology, enzymology, and medicine

“…Platensic acid ( 3 ), platensimide A (not shown) [21], homoplatensimide A ( 13 ) [22], and PTM B 1 ( 5 ), B 2 (not shown) and B 3 ( 12 ) [23] isolated from S. platensis MA7327, exhibited poor antibacterial activities underscoring the necessity of the ADHBA moiety [21]. Several natural glucoside congeners of PTM and PTN ( 15 – 19 ) have also been isolated and show no antibacterial activity (Table 1) [24–26], which is consistent with the ADHBA moiety binding in a cavity too small to accommodate an extra sugar moiety.…”

“…Initially, production titers of PTM and PTN ranged from 1 to 4 mg L −1 [15, 16], with later studies reporting up to 52 mg L −1 for PTM [30]. However, many of the natural congeners were isolated from fermentations as large as 3400 L at titers as low as 3 µg L −1 [24, 28, 29]. Semi-defined and chemically defined media for PTM production in S. platensis MA7327 have also been reported [53, 54].…”

Novonestmycins A and B, two new 32-membered bioactive macrolides from Streptomyces phytohabitans HBERC-20821

“…13 After 72 h of incubation (for a bacterial strain it was 24 h), the optical density of the medium was measured at 490 nm (OD 490 ) with a microplate reader (Thermo Scientific, Bremen, Germany). The cultural conditions were as follows: Fungi PDA medium (Potato 20%, Dextrose 2%, Agar 2%), 28°C, 72 h; Bacteria LB medium (Yeast extract 0.5%, Tryptone 1%, NaCl 1%), 37°C, 24 h.…”