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The purpose of this study was to reuse cassava wastewater (CW) for scaled-up production, via the fermentation of prodigiosin (PG), and to conduct an evaluation of its bioactivities. PG was produced at the yield of high 6150 mg/L in a 14 L-bioreactor system, when the designed novel medium (7 L), containing CW and supplemented with 0.25% casein, 0.05% MgSO 4 , and 0.1% K 2 HPO 4 , was fermented with Serratia marcescens TNU01 at 28 °C in 8 h. The PG produced and purified in this study was assayed for some medical effects and showed moderate antioxidant, high anti-NO (anti-nitric oxide), and potential α-glucosidase inhibitory activities. Notably, PG was first reported as a novel effective α-glucosidase inhibitor with a low IC50 value of 0.0183 µg/mL. The commercial anti-diabetic drug acarbose was tested for comparison and had a lesser effect with a high IC50 value of 328.4 µg/mL, respectively. In a docking study, the cation form of PG (cation-PG) was found to bind to the enzyme α-glucosidase by interacting with two prominent amino acids, ASP568 and PHE601, at the binding site on the target enzyme, creating six linkages and showing a better binding energy score (-14.6 kcal/mol) than acarbose (-10.5 kcal/mol). The results of this work suggest that cassava wastewater can serve as a low-cost raw material for the effective production of PG, a potential antidiabetic drug candidate.

Recently, microbial prodigiosin (PG) has received much attention due to its numerous beneficial applications. The aim of this study was to establish the bioprocessing of marine chitinous wastes (MCWs) for the cost-effective preparation of PG. Of the MCWs, demineralized shrimp shell powders (de-SSP) were found to be a potential source of carbon/nitrogen (C/N) for PG production by bacterial fermentation using Serratia marcescens strains. Further, PG scale-up production was investigated in a 15 L bioreactor system, and the highest yield (6200 mg/L) was achieved during fermentation using 5 L of a novel-designed culture broth that included 1.60% C/N sources (a de-SSP/casein ratio of 7/3), 0.02% K 2 SO 4, and 0.05% K 2 HPO 4 , with an initial pH of 6-7. Fermentation was conducted in the dark at 27.5 °C for 8.0 h. This study was the first to report on the utilization of shrimp wastes for cost-effective, large-scale (5 L/pilot) PG production with high productivity (6200 mg/L) in a short cultivation time. The combination of 0.02% K 2 SO 4 and 0.05% K 2 HPO 4 was also found to be a novel salt composition that significantly enhanced PG yield. The red compound was purified and confirmed as PG after analyzing its HPLC profile, mass, and UV/vis spectra. The purified PG was then tested for its bioactivities and showed effective anticancer activities, moderated antioxidant activities, and novel anti-NO effects.

This study aimed to establish the culture process for the cost-effective production of prodigiosin (PG) from demineralized crab shell powder (de-CSP), a fishery processing byproduct created via fermentation. Among the tested PG-producing strains, Serratia marcescens TNU02 was demonstrated to be the most active strain. Various ratios of protein/de-CSP were used as the sources of C/N for PG biosynthesis. The PG yield was significantly enhanced when the casein/de-CSP ratio was controlled in the range of 3/7 to 4/6. TNU02 produced PG with a high yield (5100 mg/L) in a 15 L bioreactor system containing 4.5 L of a newly-designed liquid medium containing 1.6% C/N source (protein/de-CSP ratio of 3/7), 0.02% (NH 4 ) 2 SO 4 , 0.1% K 2 HPO 4 , and an initial pH of 6.15, at 27 °C for 8 h in dark conditions. The red pigment was purified from the culture broth and then quantified as being PG by specific Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and UV spectra analysis. The purified PG demonstrated moderate antioxidant and effective inhibition against four cancerous cell lines. Notably, this study was the first to report on using crab wastes for PG bioproduction with high-level productivity (5100 mg/L) in a large scale (4.5 L per pilot) in a short period of fermentation time (8 h). The salt compositions, including (NH 4 ) 2 SO 4 and K 2 HPO 4 , were also a novel finding for the enhancement of PG yield by S. marcescens in this report.

The technology of microbial conversion provides a potential way to exploit compounds of biotechnological potential. The red pigment prodigiosin (PG) and other PG-like pigments from bacteria, majorly from Serratia marcescens , have been reported as bioactive secondary metabolites that can be used in the broad fields of agriculture, fine chemicals, and pharmacy. Increasing PG productivity by investigating the culture conditions especially the inexpensive carbon and nitrogen (C/N) sources has become an important factor for large-scale production. Investigations into the bioactivities and applications of PG and its related compounds have also been given increased attention. To save production cost, chitin and protein-containing fishery byproducts have recently been investigated as the sole C/N source for the production of PG and chitinolytic/proteolytic enzymes. This strategy provides an environmentally-friendly selection using inexpensive C/N sources to produce a high yield of PG together with chitinolytic and proteolytic enzymes by S. marcescens . The review article will provide effective references for production, bioactivity, and application of S. marcescens PG in various fields such as biocontrol agents and potential pharmaceutical drugs.

Marine chitins (MC) have been utilized for the production of vast array of bioactive products, including chitooligomers, chitinase, chitosanase, antioxidants, anti-NO, and antidiabetic compounds. The aim of this study is the bioprocessing of MC into a potent anticancer compound, prodigiosin (PG), via microbial fermentation. This bioactive compound was produced by Serratia marcescens TKU011 with the highest yield of 4.62 mg/mL at the optimal conditions of liquid medium with initial pH of 5.65-6.15 containing 1% α-chitin, 0.6% casein, 0.05% K 2 HPO 4 , and 0.1% CaSO 4 . Fermentation was kept at 25 °C for 2 d. Notably, α-chitin was newly investigated as the major potential material for PG production via fermentation; the salt CaSO 4 was also found to play the key role in the enhancement of PG yield of Serratia marcescens fermentation for the first time. PG was qualified and identified based on specific UV, MALDI-TOF MS analysis. In the biological activity tests, purified PG demonstrated potent anticancer activities against A549, Hep G2, MCF-7, and WiDr with the IC 50 values of 0.06, 0.04, 0.04, and 0.2 µg/mL, respectively. Mytomycin C, a commercial anti-cancer compound was also tested for comparison purpose, showing weaker activity with the IC 50 values of 0.11, 0.1, 0.14, and 0.15 µg/mL, respectively. As such, purified PG displayed higher 2.75-fold, 1.67-fold, and 3.25-fold efficacy than Mytomycin C against MCF-7, A549, and Hep G2, respectively. The results suggest that marine chitins are valuable sources for production of prodigiosin, a potential candidate for cancer drugs.

This report aims to characterize and reuse fish head powder (FHP) as a potential carbon/nitrogen source for microbial fermentation to produce prodigiosin (PG), and to evaluate its novel anti-fungal effect via an experimental and docking study. FHP has high protein (30.25%) and lipid (5.12%) content and a diversity of elements, which suggests that FHP is a potential substrate for microbial fermentation. Serratia marcescens TNU01 was screened as the most effective strain to produce PG from FHP. Further experiments indicated that the combination of FHP and crude chitin at the ratio of 9/1 and used at 1.5% as a C/N source for fermentation significantly enhanced PG production. Supplementing a minor amount of 0.05% Ca3(PO4)2, 0.03% K2SO4 also positively affects PG yield production. The fermentation using a bioreactor system (type of 14 L) achieved the highest PG yield production (6.4 mg/mL) in a short cultivation time (10 h) in comparison with the highest PG yield (5.8 mg/mL) obtained after 36 h of fermentation in a flask. In the anti-fungal evaluation of various plant pathogen fungal strains, PG demonstrated efficacy against Fusarium solani F04. The molecular docking results also showed that PG effectively interacted with targeting protein 3QPC of F. solani with good binding energy (DS—9.2 kcal/mol) and an acceptable RMSD value (0.94 Å). In this study, we provide a novel application of FHP for the eco-friendly production of PG, which can potentially used for the management of Fusarium solani. [ABSTRACT FROM AUTHOR]

This study aimed to reuse groundnut oil processing by-product, groundnut cake (GNC) for the low-cost production of prodigiosin (PG) via microbial technology and to assess its novel potential application for the management of black pepper nematodes. Serratia marcescens TUN02 was found as the most active PG-producing strain. Various small-scale experiments conducted in flasks indicated that GNC at 1% may be used as the sole carbon/nitrogen source for cost-effective PG production by fermentation. Notably, no further commercial ingredients and salts are required to supplement into the culture medium of this fermentation. PG was further investigated for scale-up production in a 14-L bioreactor system and PG was produced at high yield (6886 mg/L) with large-scale volume (4 L) in a short cultivation time (10 h). PG was then purified and its nematicidal activity was evaluated and showed effective inhibition of juveniles and egg hatching of Meloidogyne incognita species, harmful on black pepper, with low IC50 values of 0.2 and 0.32 mg/mL, respectively. The simple medium containing 1% GNC is the first report of cost-effective biosynthesis of PG, as well as potential in vitro anti-egg hatching activity of PG. These results indicated the potential application of GNC for low-cost bioproduction of PG for promising and novel use in the management of black pepper nematodes. [ABSTRACT FROM AUTHOR]

Marine chitins (MC) have been utilized for the production of vast array of bioactive products, including chitooligomers, chitinase, chitosanase, antioxidants, anti-NO, and antidiabetic compounds. The aim of this study is the bioprocessing of MC into a potent anticancer compound, prodigiosin (PG), via microbial fermentation. This bioactive compound was produced by Serratia marcescens TKU011 with the highest yield of 4.62 mg/mL at the optimal conditions of liquid medium with initial pH of 5.65–6.15 containing 1% α-chitin, 0.6% casein, 0.05% K2HPO4, and 0.1% CaSO4. Fermentation was kept at 25 °C for 2 d. Notably, α-chitin was newly investigated as the major potential material for PG production via fermentation; the salt CaSO4 was also found to play the key role in the enhancement of PG yield of Serratia marcescens fermentation for the first time. PG was qualified and identified based on specific UV, MALDI-TOF MS analysis. In the biological activity tests, purified PG demonstrated potent anticancer activities against A549, Hep G2, MCF-7, and WiDr with the IC50 values of 0.06, 0.04, 0.04, and 0.2 µg/mL, respectively. Mytomycin C, a commercial anti-cancer compound was also tested for comparison purpose, showing weaker activity with the IC50 values of 0.11, 0.1, 0.14, and 0.15 µg/mL, respectively. As such, purified PG displayed higher 2.75-fold, 1.67-fold, and 3.25-fold efficacy than Mytomycin C against MCF-7, A549, and Hep G2, respectively. The results suggest that marine chitins are valuable sources for production of prodigiosin, a potential candidate for cancer drugs. [ABSTRACT FROM AUTHOR]