Production of a Novel Tetrahydroxynaphthalene (THN) Derivative from Nocardia sp. CS682 by Metabolic Engineering and Its Bioactivities

Abstract

Nargenicin A1 is major secondary metabolite produced by Nocardia sp. CS682, with an effective antibacterial activity against various Gram-positive bacteria. Most Nocardia spp. have metabolic ability to produce compounds of diverse nature, so one-strain-many-compounds (OSMAC) approach can be applied for obtaining versatile compounds from these strains. In this study, we characterized a novel 1, 3, 6, 8-tetrahydroxynaphthalene (THN) derivative by metabolic engineering approach leading to the inactivation of nargenicin A1 biosynthesis. By using genome mining, metabolite profiling, and bioinformatics, the biosynthetic gene cluster and biosynthetic mechanism were elucidated. Further, the antibacterial, anticancer, melanin formation, and UV protective properties for isolated THN compound were performed. The compound did not exhibit significant antibacterial and cytotoxic activities, but it exhibited promising UV protection effects. Thus, metabolic engineering is an effective strategy for discovering novel bioactive molecules.

Characterization of Tailoring Steps of Nargenicin A1 Biosynthesis Reveals a Novel Analogue with Anticancer Activities

“…The culture and genetic manipulation of Nocardia sp. CS682 were performed according to previous protocols. , DD medium containing 0.2% oatmeal, 0.2% yeast extract, 0.2% soybean meal, 0.1% calcium chloride, 1% maltose, 0.1% magnesium chloride, and 0.4% glycerol was used as the production medium. The antibiotics were added when necessary at the following concentrations: 50 μg/mL for apramycin, 100 μg/mL for ampicillin, and 150 μg/mL for thiostrepton.…”

“…Wild type strain Nocardia sp. CS682 (positive control), S. venezuelae /pCAP03-nar (producer), and S. venezuelae /pCAP03 (negative control) were grown in DD1 medium (DD medium supplemented with 0.05% MgCl 2 , 0.01% l -methionine, and 0.1% FeCl 3 ) for 6 days. The cultures were centrifuged, and the supernatant was extracted with ethyl acetate.…”

Complete Genome Sequence of Nocardia sp. Strain CS682, a Producer of Antibacterial Compound Nargenicin A1

“…strain CS682 is nargenicin A1, an antibacterial polyketide with promising activity against various Gram-positive pathogenic bacteria (3). Similarly, IBR-3, a novel tetrahydroxynaphthalene (THN) derivative with UV protection effects, was also isolated from strain CS682 (4).…”

Heterologous production of cyanobacterial compounds

“…Peptide molecules are biosynthesized from both nonribosomal and ribosomal origins through the actions of nonribosomal peptide synthetases (NRPSs) and ribosomally synthesized and post-translationally modified peptides (RiPPs) biosynthetic machinery, respectively (Sieber & Marahiel, 2005 ; Ortega & van der Donk, 2016 ; Hudson & Mitchell, 2018 ). Similarly, acyl-CoA building blocks are processed through sequential decarboxylative condensations by polyketide synthases (PKSs) to generate PKs (Dhakal et al., 2019 ; Smith & Tsai, 2007 ; Mishra et al., 2019 ). Furthermore, some cyanobacterial NPs are derived from hybrid biosynthetic systems.…”