Marine Rare Actinobacteria: Isolation, Characterization, and Strategies for Harnessing Bioactive Compounds

Actinobacteria are prolific producers of thousands of biologically active natural compounds with diverse activities. More than half of these bioactive compounds have been isolated from members belonging to actinobacteria. Recently, rare actinobacteria existing at different environmental settings such as high altitudes, volcanic areas, and marine environment have attracted attention. It has been speculated that physiological or biochemical pressures under such harsh environmental conditions can lead to the production of diversified natural compounds. Hence, marine environment has been focused for the discovery of novel natural products with biological potency. Many novel and promising bioactive compounds with versatile medicinal, industrial, or agricultural uses have been isolated and characterized. The natural compounds cannot be directly used as drug or other purposes, so they are structurally modified and diversified to ameliorate their biological or chemical properties. Versatile synthetic biological tools, metabolic engineering techniques, and chemical synthesis platform can be used to assist such structural modification. This review summarizes the latest studies on marine rare actinobacteria and their natural products with focus on recent approaches for structural and functional diversification of such microbial chemicals for attaining better applications

Enzymatically Synthesized Ginsenoside Exhibits Antiproliferative Activity in Various Cancer Cell Lines

A glycoside derivative of compound K (CK) was synthesized by using a glycosyltransferase, and its biological activity was tested against various cancer-cell lines. A regiospecific, β-1,4-galactosyltransferase (LgtB) converted 100% of 0.5 mmol CK into a galactosylated product in 3 h. The structure of the synthesized derivative was revealed with high performance liquid chromatography, mass spectroscopy, as well as nuclear magnetic resonance analyses, and it was recognized as 20-O-β-D-lactopyranosyl-20(S)-protopanaxadiol (CKGal). Out of the four cancer-cell lines tested (gastric carcinoma (AGS), skin melanoma (B16F10), cervical carcinoma (HeLa), and brain carcinoma (U87MG)), CKGal showed the best cytotoxic ability against B16F10 and AGS when compared to other ginsenosides like compound K (20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol), Rh2 (3-O-β-D-glucopyranosyl-20(S)-protopanaxadiol), and F12 (3-O-β-D-glucopyranosyl-12-O-β-D-glucopyranosyl-20(S)-protopanaxadiol). Thus, the synthesized derivative (CKGal) is a pharmacologically active ginsenoside

One-Pot Multienzyme Cofactors Recycling (OPME-CR) System for Lactose and Non-natural Saccharide Conjugated Polyphenol Production

A one-pot multienzyme cofactors recycling (OPME-CR) system was designed for the synthesis of UDP-α-d-galactose, which was combined with LgtB, a β-(1,4) galactosyltransferase from <i>Neisseria meningitidis</i>, to modify various polyphenol glycosides. This system recycles one mole of ADP and one mole of UDP to regenerate one mole of UDP-α-d-galactose by consuming two moles of acetylphosphate and one mole of d-galactose in each cycle. The ATP additionally used to generate UDP from UMP was also recycled at the beginning of the reaction. The engineered cofactors recycling system with LgtB efficiently added a d-galactose unit to a variety of sugar units such as d-glucose, rutinose, and 2-deoxy-d-glucose. The temperature, pH, incubation time, and divalent metal ions for the OPME-CR system were optimized. The maximum number of UDP-α-d-galactose regeneration cycles (RC_max) was 18.24 by fed batch reaction. The engineered system generated natural and non-natural polyphenol saccharides efficiently and cost-effectively

Enzymatic synthesis of novel quercetin sialyllactoside derivatives

<p>Quercetin and its derivatives are important flavonols that show diverse biological activity, such as antioxidant, anticarcinogenic, anti-inflammatory, and antiviral activities. Adding different substituents to quercetin may change the biochemical activity and bioavailability of molecules, when compared to the aglycone. Here, we have synthesised two novel derivatives of quercetin, quercetin-3-<i>O</i>-<i>β</i>-d-glucopyranosyl, 4′′-<i>O</i>-d-galactopyranosyl 3′′′-<i>O</i>-<i>α</i>-<i>N</i>-acetyl neuraminic acid i.e. 3′-sialyllactosyl quercetin (3′SL-Q) and quercetin-3-<i>O</i>-<i>β</i>-d-glucopyranosyl, 4′′-<i>O</i>-<i>β</i>-d-galactopyranosyl 6′′′-<i>O</i>-<i>α</i>-<i>N</i>-acetyl neuraminic acid i.e. 6′-sialyllactosyl quercetin (6′SL-Q) with the use of glycosyltransferases and sialyltransferases enzymes. These derivatives of quercetin were characterised by high-resolution quadrupole-time-of-flight electrospray ionisation mass spectrometry (HR-QTOF-ESI/MS) and ¹H and ¹³C nuclear magnetic resonance (NMR) analyses.</p