Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from <i>Gephyromycinifex aptenodytis</i> gen. nov., sp. nov.

Wen-Zhuo Zhu; Shu-Heng Wang; Hui-Min Gao; Ya-Ming Ge; Jun Dai; Xiao-Ling Zhang; Qiao Yang

doi:10.3390/md20010034

Marine Drugs (Dec 2021)

Characterization of Bioactivities and Biosynthesis of Angucycline/Angucyclinone Derivatives Derived from <i>Gephyromycinifex aptenodytis</i> gen. nov., sp. nov.

Wen-Zhuo Zhu,
Shu-Heng Wang,
Hui-Min Gao,
Ya-Ming Ge,
Jun Dai,
Xiao-Ling Zhang,
Qiao Yang

Affiliations

Wen-Zhuo Zhu: Department of Marine Chemistry, College of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China
Shu-Heng Wang: Department of Marine Chemistry, College of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China
Hui-Min Gao: Department of Marine Chemistry, College of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China
Ya-Ming Ge: National Engineering Research Center for Marine Aquaculture, Zhejiang Ocean University, Zhoushan 316021, China
Jun Dai: Natural “111” Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), College of Bioengineering, Hubei University of Technology, Wuhan 430068, China
Xiao-Ling Zhang: Department of Marine Chemistry, College of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China
Qiao Yang: Department of Marine Chemistry, College of Marine Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China

DOI: https://doi.org/10.3390/md20010034
Journal volume & issue: Vol. 20, no. 1
p. 34

Abstract

Read online

Strain NJES-13T is the type strain and currently the only species of the newly established actinobacteria genera Aptenodytes in the family Dermatophilaceae isolated from the gut microbiota of the Antarctic emperor penguin. This strain demonstrated excellent bioflocculation activity with bacteria-derived exopolysaccharides (EPSs). Moreover, it produced bioactive angucycline/angucyclinone derivatives (ADs) and contained one type III polyketide synthase (T3PKS), thus demonstrating great potential to produce novel bioactive compounds. However, the low productivity of the potential new AD metabolite was the main obstacle for its chemical structure elucidation. In this study, to increase the concentration of targeted metabolites, the influence of cellular morphology on AD metabolism in strain NJES-13T was determined using glass bead-enhanced fermentation. Based on the cellular ultra-structural observation driven by bacterial EPSs, and quantitative analysis of the targeted metabolites, the successful increasing of the productivity of three AD metabolites was achieved. Afterward, a new frigocyclinone analogue was isolated and then identified as 2-hydroxy-frigocyclinone, as well as two other known ADs named 2-hydroxy-tetrangomycin (2-HT) and gephyromycin (GPM). Three AD metabolites were found to demonstrate different bioactivities. Both C-2 hydroxyl substitutes, 2-hydroxy-tetrangomycin and 2-hydroxy-frigocyclinone, exhibited variable inhibitory activities against Staphylococcus aureus, Bacillus subtilis and Candida albicans. Moreover, the newly identified 2-hydroxy-frigocyclinone also showed significant cytotoxicity against three tested human-derived cancerous cell lines (HL-60, Bel-7402 and A549), with all obtained IC50 values less than 10 µM. Based on the genetic analysis after genomic mining, the plausible biogenetic pathway of the three bioactive ADs in strain NJES-13T was also proposed.

Published in Marine Drugs

ISSN: 1660-3397 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: http://www.mdpi.com/journal/marinedrugs

About the journal

Abstract

Keywords