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•Cultivation conditions and strategies for lutein production are summarized.•Metabolic and genetic designs for lutein biosynthesis are discussed.•Two-stage strategy is efficient in ...enhancing lutein productivity.•The in-situ lutein accumulation in fermenters is suggested to lower costs.
Lutein production from microalgae is a sustainable and economical strategy to offer the increasing global demands, but is still challenged with low lutein content at the high-cell density for commercial production. This review summarizes the suitable conditions for cell growth and lutein accumulation, and presents recent cultivation strategies to further improve lutein productivity. Light and nitrogen play critical roles in lutein biosynthesis that lead to the efficient multi-stage cultivation by increasing lutein content at the later stage. In addition, metabolic and genetic designs for carbon regulation and lutein biosynthesis are discussed at the molecule level. The in-situ lutein accumulation in fermenters by regulating carbon metabolism is considered as a cost-effective direction. Then, downstream processes are summarized for the efficient lutein recovery. Finally, challenges of current lutein production from microalgae are discussed. Meanwhile, potential solutions are proposed to improve lutein content and drive down costs of microalgal biomass.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Continuous processing (CP) is delivering new efficiencies in biomanufacturing.•The traditional focus on antibodies is being broadened to other biopharmaceuticals.•CP can leap biomanufacturing into ...the 21stC cementing it as an advanced industry.•A process systems approach to integrated continuous bioprocess design is required.•Further research is urgently needed to accelerate this new paradigm.
Continuous production delivers higher productivity and better quality than traditional batch-wise approaches. It intensifies production lowering capital cost and enables better control. Despite obvious advantages, continuous processing has not yet guided biomanufacturing to 21st Century Advanced Manufacturing status. Production relies primarily on batch-wise methods that have served the industry through its infancy. While great improvements have been achieved on the upstream side, downstream processing lacks development in continuous processing and is now the handbrake on modernisation. Nevertheless, there are hopeful advances. Research on continuous chromatographic purification for antibodies is maturing, and work has commenced on other unit operations and on process system integration. This exciting field of process intensification research is at a turning point, though considerably more research is needed. This review aims to summarize the latest developments and capabilities of continuous downstream processing applied in biopharmaceutical research and gives an overview of recent developments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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•Cysteine-modified PEG-K3PO4 ATPS was formulated for laccase purification.•Highly efficient 3D-printed micro-mixer and phase separator were fabricated.•Continuous ATPS boosts ...partition coefficient & extraction efficiency significantly.•Continuous/autonomous separation by computer vision guided interphase monitoring.•Enhanced partitioning of enzyme was depicted in low-abundance and real matrix.
Downstream processing of biomolecules, particularly therapeutic proteins and enzymes, presents a formidable challenge due to intricate unit operations and high costs. This study introduces a novel cysteine (cys) functionalized aqueous two-phase system (ATPS) utilizing polyethylene glycol (PEG) and potassium phosphate, referred as PEG-K3PO4/cys, for selective extraction of laccase from complex protein mixtures. A 3D-baffle micro-mixer and phase separator was meticulously designed and equipped with computer vision controller, to enable precise mixing and continuous phase separation under automated-flow. Microfluidic-assisted ATPS exhibits substantial increase in partition coefficient (Kflow = 16.3) and extraction efficiency (EEflow = 88 %) for laccase compared to conventional batch process. Integrated and continuous-flow process efficiently partitioned laccase, even in low concentrations and complex crude extracts. Circular dichroism spectra of laccase confirm structural stability of enzyme throughout the purification process. Eventually, continuous-flow microfluidic bioseparation is highly useful for seamless downstream processing of target biopharmaceuticals in integrated and autonomous manner.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite receiving increasing attention during the last few decades, the production of microalgal biofuels is not yet sufficiently cost-effective to compete with that of petroleum-based conventional ...fuels. Among the steps required for the production of microalgal biofuels, the harvest of the microalgal biomass and the extraction of lipids from microalgae are two of the most expensive. In this review article, we surveyed a substantial amount of previous work in microalgal harvesting and lipid extraction to highlight recent progress in these areas. We also discuss new developments in the biodiesel conversion technology due to the importance of the connectivity of this step with the lipid extraction process. Furthermore, we propose possible future directions for technological or process improvements that will directly affect the final production costs of microalgal biomass-based biofuels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The conversion of renewable biomass feedstock into value-added products via bioprocessing platforms has become attractive because of environmental and health concerns. Process performance and cost ...competitiveness are major factors in the bioprocess design to produce desirable products from biomass feedstock. Proper pretreatment allows delignification and hemicellulose removal from the liquid fraction, allowing cellulose to be readily hydrolyzed to monomeric sugars. Several industrial products are produced via sugar fermentation using either naturally isolated or genetically modified microbes. Microbial platforms play an important role in the synthesis of several products, including drop-in chemicals, as-in products, and novel compounds. The key elements in developing a fermentation platform are medium formulation, sterilization, and active cells for inoculation. Downstream bioproduct recovery may seem like a straightforward chemical process, but is more complex, wherein cost competitiveness versus recovery performance becomes a challenge. This review summarizes the prospects for utilizing renewable biomass for bioprocessing.
•Converting renewable biomass to high-value products via bioprocesses is attractive.•Proper pretreatment allows lignin and hemicellulose removal and cellulose recovery.•Microbial fermentation is the platform to produce industrial products from biomass.•Downstream recovery of bioproducts is like the chemical process but more complexed.•High process cost is key limitation of bioprocess compared with chemical technology.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The objective of the study is to evaluate the potential usage of fresh coconut inflorescence sap (FCIS) as a fermentation medium for levan production using Bacillus subtilis. The fermentation ...conditions such as temperature, pH and agitation speed were optimized using Response Surface Methodology (RSM). The levan yield was enhanced by optimizing the downstream process by altering the pH (5–12) with different solvents (Ethanol, Methanol and Isopropanol) at different ratios. The yield was enhanced further by fed batch fermentation process by feeding with sucrose alone or sucrose and yeast extract. The maximum levan yield was observed as 51.84 g/L at the optimized conditions (Temperature - 35 °C, pH 6.5, and Agitation speed - 150 rpm) using Response Surface Methodology. Whereas, in fed-batch fermentation process the levan yield was increased to 62.1 g/L. The maximum levan was obtained at pH 10 with ethanol at 1:5 ratio. The obtained levan was characterised and confirmed by TLC, FTIR, NMR and GPC analysis. To best of our knowledge, this is the first study conducted to produce levan from FCIS and results showed that FCIS can be a natural low-cost substrate for levan production.
•Levan is a natural microbial polysaccharide used as an alternative for synthetic sweetener.•FCIS as a natural substrate for levan production and optimized by RSM and fed-batch method.•The composition of the culture media is (i) FCIS (ii) FCIS + 2.0 g sucrose (iii) FCIS + 1.5 g sucrose + 0.5 g yeast extract.•Different ratio of ethanol, methanol and isopropanol were used for downstream process.•FTIR, NMR and GPC analysis confirmed the integrity of obtained levan.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•A simple and economical process for downstream of lactic acid has been developed.•The pH of the extraction medium was critical during lactic acid purification.•Optimized downstream process ...conditions resulted in a yield of 86% and 93% purity.•The purified lactic acid was further characterized by FTIR and NMR.
Lactic acid is one of the essential platform chemicals, and despite the availability of a range of downstream processes, its effective recovery is still elusive. A phase partitioning process using n-butanol and a chaotropic salt ammonium sulphate was developed to recover lactic acid from the fermentation broth of Lactobacillus pentosus SKL-18. During the optimization of various process parameters, the extraction medium's pH was found to be critical, with 2.5 being the best. The optimized process resulted in a lactic acid yield of 86% and found it to be 93% pure. The purity and characteristics of lactic acid were confirmed by FTIR and NMR spectra. This solvent-based extraction procedure is an economical and straightforward downstream process for purifying lactic acid produced from agro- and bakery-residues. The pure lactic acid can further be used for enzymatic synthesis of high value-added product PLA, a biodegradable and biocompatible plastics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Currently, growing attention is being devoted to the conversion of biomass into value-added products, such as itaconic acid (IA), which is considered as the cleanest alternative to petroleum-based ...acrylic acid. IA is an unsaturated dicarboxylic acid that is used as a building block chemical for the production of several value-added products such as poly-itaconic acid. IA and its derivatives have a wide range of potential applications in textile, paint, pharmaceutical and chemical industries. Presently, industries are producing IA on the large scale by fermentation from glucose. However, due to the primary utility of glucose as a food, it cannot meet the global demand for IA production in an economical way. The main challenge, so far, has been the production technology, which does not support cost-effective and competitive production of IA. This review discusses the various bottlenecks faced during each step of IA production, along with possible remedies to deal with these problems. Furthermore, it reviews the recent progress in fermentative IA production and sheds light on different microorganisms used, potential substrates and fermentation conditions. The review also covers market potential for IA, which indicates that IA can be produced cost-effectively from sustainable substrates, and it has the potential to replace petrochemicals in the near future.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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•High lignin precipitation yields using n-pentane as antisolvent.•Marginal loss of the antisolvent n-pentane due to efficient recovery.•Analysis of solubility data regarding optimum ...antisolvent/feed ratio is beneficial.•Reduced energy consumption due to concentration of lignin prior to precipitation.
For the sustainable production of chemicals, lignocellulosic biomass can be fractionated into cellulose, hemicellulose and lignin, which can be subsequently converted into valuable intermediates. In the OrganoCat pulping process, lignin is separated from other fractionation products by in situ extraction into the organic solvent 2-methyltetrahydrofuran. However, a suitable concept for the subsequent separation of lignin from this solvent has not yet been identified. In this work, a technically feasible process for the separation of lignin from 2-methyltetrahydrofuran solutions using antisolvent precipitation is developed and evaluated based on lignin precipitation yield, solvent recovery and energy efficiency. For the determination of suitable antisolvents, an experimental solvent screening is performed. The conceptual process design is accomplished on the basis of lignin solubility measurements and process simulations. High lignin precipitation yields are achieved using n-hexane and n-pentane. An efficient process for lignin separation by combining solvent evaporation and precipitation using n-pentane is presented. The proposed separation process leads to lignin which can be separated by filtration and is characterized by low energy consumption and effective antisolvent recovery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The rapid increase of CO2 concentration in the atmosphere combined with depleted supplies of fossil fuels has led to an increased commercial interest in renewable fuels. Due to their high biomass ...productivity, rapid lipid accumulation, and ability to survive in saline water, microalgae have been identified as promising feedstocks for industrial-scale production of carbon-neutral biodiesel. This study examines the principles involved in lipid extraction from microalgal cells, a crucial downstream processing step in the production of microalgal biodiesel. We analyze the different technological options currently available for laboratory-scale microalgal lipid extraction, with a primary focus on the prospect of organic solvent and supercritical fluid extraction. The study also provides an assessment of recent breakthroughs in this rapidly developing field and reports on the suitability of microalgal lipid compositions for biodiesel conversion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
