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

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.

Download Full-text

Ectopic expression and functional characterization of type III polyketide synthase mutants from Emblica officinalis Gaertn

Plant Cell Reports ◽

10.1007/s00299-016-2020-0 ◽

2016 ◽

Vol 35 (10) ◽

pp. 2077-2090 ◽

Cited By ~ 2

Author(s):

Girija Aiswarya ◽

Vijayanathan Mallika ◽

Luis A. J. Mur ◽

Eppurathu Vasudevan Soniya

Keyword(s):

Polyketide Synthase ◽

Functional Characterization ◽

Ectopic Expression ◽

Emblica Officinalis ◽

Type Iii Polyketide Synthase ◽

Type Iii

Download Full-text

Characterization of the Substrate Specificity of PhlD, a Type III Polyketide Synthase fromPseudomonas fluorescens

Journal of Biological Chemistry ◽

10.1074/jbc.m606500200 ◽

2006 ◽

Vol 281 (42) ◽

pp. 32036-32047 ◽

Cited By ~ 47

Author(s):

Wenjuan Zha ◽

Sheryl B. Rubin-Pitel ◽

Huimin Zhao

Keyword(s):

Substrate Specificity ◽

Polyketide Synthase ◽

Type Iii Polyketide Synthase ◽

Type Iii

Download Full-text

Characterization of the Substrate Specificity of PhlD, a Type III Polyketide Synthase from Pseudomonas fluorescens

Journal of Biological Chemistry ◽

10.1016/s0021-9258(19)84117-0 ◽

2006 ◽

Vol 281 (42) ◽

pp. 32036-32047

Author(s):

Wenjuan Zha ◽

Sheryl B. Rubin-Pitel ◽

Huimin Zhao

Keyword(s):

Substrate Specificity ◽

Pseudomonas Fluorescens ◽

Polyketide Synthase ◽

Type Iii Polyketide Synthase ◽

Type Iii

Download Full-text

CHARACTERIZATION OF MONOHEADED TRYPSIN INHIBITORS FROM THE SEEDS OF ABELMOSCHUS MOSCHATUS L.

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i12.28735 ◽

2018 ◽

Vol 11 (12) ◽

pp. 459

Author(s):

Muni Kumar Dokka ◽

Hemalatha K. P. J ◽

Siva Prasad Davuluri

Keyword(s):

Chemical Modification ◽

Mode Of Action ◽

Physiological Role ◽

Trypsin Inhibitors ◽

Control Mechanisms ◽

Bovine Trypsin ◽

Ic50 Values ◽

Arginine Residues ◽

Inhibitory Activities

Objective: The objective of the present study was to characterize the monoheaded trypsin inhibitors, Abelmoschus moschatus trypsin inhibitor-I (AMTI-I) and AMTI-II from the seeds of A. moschatus with respect to their specificity, mode of action, and active site residues.Methods: Standard methods were followed in determining inhibitory activities of monoheaded inhibitors. IC50 values and inhibitory constants (Ki) of AMTI-I and AMTI-II were determined. Studies on complex formation and chemical modification of inhibitors were performed.Results: AMTI-I and AMTI-II were found to be serpins, strongly active against trypsin, moderately active against porcine elastase, Staphylococcus aureus protease, and Aspergillus oryzae protease. AMTI-I and AMTI-II have shown non-competitive type of inhibition toward bovine trypsin with Ki values of inhibitors for trypsin found to be 0.25±0.02 nM and 0.22±0.06 nM, respectively. Complex studies revealed the formation of stable 1:1 complex of trypsin with both AMTI-I and AMTI-II. Chemical modification of the functional groups of the inhibitors by selective reagents indicated that arginine residues are essential for their trypsin inhibitory activities.Conclusion: Investigations on the specificity of protease inhibitors are important for understanding their physiological role, control mechanisms involved in the regulation of proteolysis in biological systems and mode of action.

Download Full-text