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

Abstract

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.

Taxonomic and Bioactivity Characterizations of Mameliella alba Strain LZ-28 Isolated from Highly Toxic Marine Dinoflagellate Alexandrium catenella LZT09

“…Bacterial exopolysaccharides (EPSs) were revealed to serve as one essential chemical intermedia within the microscopic phycosphere niches and mediate host–microbe interactions [ 2 , 3 , 4 , 5 , 53 ]. During our previous investigations, several novel bacterial species, which produce bioactive EPSs, were also recovered from the freshwater [ 26 ] and marine phycosphere [ 27 , 28 , 29 , 30 , 31 ], as well as the gut microbiota of Antarctic emperor penguin [ 48 , 54 , 55 ]. In this study, the preliminary experiment showed that temperature and carbon sources were the main two factors influencing the bacterial growth and EPS accumulation.…”

“…In addition, the genomic mining also revealed the presence of several typical biosynthesis genes (wzx, exo, and muc) for bacterial EPS biosynthesis in strain LZ-28. Thus, the present study indicated that strain LZ-28 could serve as a new, fresh bacterial candidate with natural potential for the production of versatile EPS bioflocculants derived from marine microalgae with potential pharmaceutical, environmental, and biotechnological implications [ 27 , 28 , 29 , 30 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ].…”

“…The preparation of the transmission electron microscopy (TEM) sample was performed using the negative-staining method [ 54 , 55 ]. Briefly, vegetative cells of strain LZ-28 were observed from a fresh, 24 h culture inoculated in MB.…”

Marine natural products

“…8 Continuing work on Gephyromycinifex aptenodytis derived from the gut microbiota of the Antarctic emperor penguin, Aptenodytes forsteri yielded an additional new angucyclinone analogue, 2-hydroxy-frigocyclinone 20 . 9 An aromatic glycoside 21 was identified from a sediment-derived collection of Nocardiopsis synnemataformans 10 and four new fluvirucin-type macrolactams, fluvirucins B7–B10 22 – 25 were isolated from a sponge-derived rare actinomycete Nonomuraea sp. 11 …”

Marine Compounds with Anti-Candida sp. Activity: A Promised “Land” for New Antifungals

“…For example, the NJES-13T, an actinobacterial strain present in its gut microbiota, is a producer of anguciclinone, gepyromycin (GPM), and 2-hydroxy-tetrangomycin (2-HT), as well as complex bioflocculation active exopolysaccharide (EPS) metabolites. It was observed the angucycline/angucyclinone derivative metabolites have been isolated from this strain with inhibitory activity against the microorganisms Staphylococcus aureus , Bacillus subtilis , and C. albicans [ 44 ]. Similarly, some strains of Aspergillus sp.…”