Biosynthesis of nitrogen-containing natural products, C7N aminocyclitols and bis-indoles, from actinomycetes

Abstract

Actinomycetes are a major source of bioactive natural products with important pharmaceutical properties. Understanding the natural enzymatic assembly of complex small molecules is important for rational metabolic pathway design to produce "artificial" natural products in bacterial cells. This review will highlight current research on the biosynthetic mechanisms of two classes of nitrogen-containing natural products, CN aminocyclitols and bis-indoles. Validamycin A is a member of CN aminocyclitol natural products from Streptomyces hygroscopicus. Here, two important biosynthetic steps, pseudoglycosyltranferase-catalyzed C-N bond formation, and C-sugar phosphate cyclase-catalyzed divergent carbasugar formation, will be reviewed. In addition, the bis-indolic natural products indolocarbazole, staurosporine from Streptomyces sp. TP-A0274, and rearranged bis-indole violacein from Chromobacterium violaceum are reviewed including the oxidative course of the assembly pathway for the bis-indolic scaffold. The identified biosynthesis mechanisms will be useful to generating new biocatalytic tools and bioactive compounds.

Microorganisms: A Potential Source of Bioactive molecules for Antioxidants and Antimicrobial Applications

“…After 16S rRNA sequences, it is confirmed that NPS12745 is a innovative strain of genus Marinispora, which produced ample of new chlorinated bisindole pyrroles and lynamicins A-E. The bisindole pyrrole derivatives include chromopyrrolic acid, earlier isolated from Chromobacterium violaceum [26]. The first halogenated bisindole derivative was Lynamicins A-E, having antibacterial activity against a panel of Gram + and Grambacteria, i.e., MSSA, MRSA: methicillin-resistant S. aureus, Staphylococcus epidermidis and Enterococcus faecalis, signifying possible cure of nosocomial infections [27].…”

A severe leakage of intermediates to shunt products in acarbose biosynthesis

“…The supernatant of fermentation broth was obtained by centrifugation at 15,777 × g for 10 min and diluted for 5 folds. The concentration of 1 was analyzed by HPLC (Agilent series 1260, Agilent Technologies, USA) with Agilent ZORBAX NH 2 column (4.6 × 250 mm 2 Supplementary Table 10.…”

“…T he α-glucosidase inhibitor acarbose (1) is one of the prominent representatives of C 7 N-aminocyclitol-containing natural products and has been used for the clinical treatment of type 2 diabetes mellitus since it was introduced to the market in 1990 1,2 . This pseudosugar-containing oligosaccharide has competitive inhibitory activities toward intestinal maltase, sucrase, dextrinase, and glucoamylase, and thereby delays carbohydrate absorption and controls postprandial hyperglycemia 1,3 .…”

Total Syntheses of Kirkamide and N‐acetyl ent‐Conduramine B‐1

“…[6] These structural motifs have been shown different biological activities including therapeutic and agrochemical. [7] For instance, acarbose and validamycin generally used to control diabetes and sheath bright of rice plant. The key structural motif present in these molecules is unsaturated aminocyclitol moiety valienamine (Figure 1).…”

“…C 7 N‐aminocyclitol analogues are one of the important amino carbasugars of aminocyclitols and these derivatives having exocyclic methyl or hydroxymethyl substituent [6] . These structural motifs have been shown different biological activities including therapeutic and agrochemical [7] . For instance, acarbose and validamycin generally used to control diabetes and sheath bright of rice plant.…”