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.
Highlights
Natural products (NP)s from microorganisms, plants, and higher organisms are important sources of antimicrobials and anti-tumor agents used in drug development [1,2,3]
Depending on the structures of the products, bacterial type III polyketide synthases (PKSs) are categorized into five groups: PhlD from Pseudomonas fluorescens generating phloroglucinol, DpgA from Amycolatopsis major five groups: PhlD from Pseudomonas fluorescens generating phloroglucinol, DpgA from orientalis producing 3,5-dihydroxyphenylglycine (DHPG), SrsA from Streptomyces griseus generating
Nargenicin A1, with promising antibacterial activity against various Gram positive bacteria including methicillin resistant Staphylococcus aureus (MRSA), is major secondary metabolite produced by Nocardia sp
Summary
Natural products (NP)s from microorganisms, plants, and higher organisms are important sources of antimicrobials and anti-tumor agents used in drug development [1,2,3]. The most crucial step in the mechanistic differences, all types of PKS compounds are biosynthesized by sequential decarboxylative biosynthesis of such compounds is the formation of C–C bonds present in the molecular backbone condensation of acyl-CoA precursors. Type III PKS alone is responsible for the formation of C–C bonds through a complete series confined with a single active site [18]. Depending on the structures of the products, bacterial type III PKSs are categorized into major. Depending on the structures of the products, bacterial type III PKSs are categorized into five groups: PhlD from Pseudomonas fluorescens generating phloroglucinol, DpgA from Amycolatopsis major five groups: PhlD from Pseudomonas fluorescens generating phloroglucinol, DpgA from orientalis producing 3,5-dihydroxyphenylglycine (DHPG), SrsA from Streptomyces griseus generating. The biological importance of this compound was assessed by evaluating its antibacterial, anticancer, melanin formation, and UV-protectant activities
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