Biocatalysis: applications and potentials for the chemical industry

The chemical industry is exploring the use of renewable feed stocks to improve sustainability, prompting the exploration of bioprocesses for the production of chemicals. Attractive features of biological systems include versatility, substrate selectivity, regioselectivity, chemoselectivity, enantioselectivity and catalysis at ambient temperatures and pressures. However, a challenge facing bioprocesses is cost competitiveness with chemical processes because capital assets associated with the existing commercial processes are high. The chemical industry will probably use biotechnology with existing feed stocks and processes to extract higher values from feed stocks, process by-products and waste streams. In this decade, bioprocesses that offer either a process or a product advantage over traditional chemical routes will become more widely used.     

红外光谱技术在生物过程监测中的应用

在线监测化学组分的浓度对许多生物过程都是十分必要的。然而,探头需耐高温灭菌的要求和生物体系自身的复杂性给许多分析技术的在线监测带来了困难。近几年,随仪器和数据处理技术的迅速发展,应用红外光谱技术对生物过程的原位或在线监测日益广泛。本文对红外过程分析技术进行了较全面的综述,介绍了红外分析的原理、进展及在生物过程监测中的应用。     

Hybrid electrosynthesis as non-genetic approach for regulating microbial metabolism towards waste valorization in circular framework

Biogenic waste (solid/liquid/gaseous) utilization in biological processes has disruptive potential of inclining towards carbon neutrality, while producing diverse products output. Anaerobic fermentation (methanogenesis and acidogenesis) routes are crucial bioprocesses for production of various renewable chemicals (carboxylate platform/organic acids, short/medium chain alcohols, aldehydes, biopolymers) and fuels (methane, hydrogen, hythane, biodiesel and electricity), while individual operations posing process limitations on their conversion efficiency. Advantageous benefit of using the individual bioprocess technicalities is of utmost importance in the context of sustainability to conceptualize and execute integrated waste biorefinery. The opinion article intends to document/familiarize the waste-fed biorefinery potential with application of hybrid advancements towards multiple product/energy/renewable chemical spectrum leading to carbon neutrality bioprocesses. Unique and notable challenges with diverse process integrations along with electrochemical/interspecies-redox metabolites-materials synergy/enzymatic interventions are specifically emphasized on application-oriented waste feedstock potential towards achieving sustainability.     

Oxidative fermentations and exopolysaccharides production by acetic acid bacteria: a mini review

Acetic acid bacteria are versatile organisms converting a number of carbon sources into biomolecules of industrial interest. Such properties, together with the need to limit chemical syntheses in favor of more sustainable biological processes, make acetic acid bacteria appropriate organisms for food, chemical, medical, pharmaceutical and engineering applications. At current, well-established bioprocesses by acetic acid bacteria are those derived from the oxidative pathways that lead to organic acids, ketones and sugar derivates. Whereas emerging applications include biopolymers, such as bacterial cellulose and fructans, which are getting an increasing interest for the biotechnological industry. However, considering the industrial demand of high performing bioprocesses, the production yield of metabolites obtained by acetic acid bacteria, is still not satisfying. In this paper we review the major acetic acid bacteria industrial applications, considering the current status of bioprocesses. We will also describe new biotechnological advances in order to optimize the industrial production, offering also an overview on future directions.     

New challenges and opportunities for industrial biotechnology

ABSTRACT: Industrial biotechnology has not developed as fast as expected due to some challenges including the emergences of alternative energy sources, especially shale gas, natural gas hydrate (or gas hydrate) and sand oil et al. The weaknesses of microbial or enzymatic processes compared with the chemical processing also make industrial biotech products less competitive with the chemical ones. However, many opportunities are still there if industrial biotech processes can be as similar as the chemical ones. Taking advantages of the molecular biology and synthetic biology methods as well as changing process patterns, we can develop bioprocesses as competitive as chemical ones, these including the minimized cells, open and continuous fermentation processes et al.     

Biochemistry,genetics and biotechnology of glycerol utilization in Pseudomonas species

The use of renewable waste feedstocks is an environment-friendly choice contributing to the reduction of waste treatment costs and increasing the economic value of industrial by-products. Glycerol (1,2,3-propanetriol), a simple polyol compound widely distributed in biological systems, constitutes a prime example of a relatively cheap and readily available substrate to be used in bioprocesses. Extensively exploited as an ingredient in the food and pharmaceutical industries, glycerol is also the main by-product of biodiesel production, which has resulted in a progressive drop in substrate price over the years. Consequently, glycerol has become an attractive substrate in biotechnology, and several chemical commodities currently produced from petroleum have been shown to be obtained from this polyol using whole-cell biocatalysts with both wild-type and engineered bacterial strains. Pseudomonas species, endowed with a versatile and rich metabolism, have been adopted for the conversion of glycerol into value-added products (ranging from simple molecules to structurally complex biopolymers, e.g. polyhydroxyalkanoates), and a number of metabolic engineering strategies have been deployed to increase the number of applications of glycerol as a cost-effective substrate. The unique genetic and metabolic features of glycerol-grown Pseudomonas are presented in this review, along with relevant examples of bioprocesses based on this substrate – and the synthetic biology and metabolic engineering strategies implemented in bacteria of this genus aimed at glycerol valorization.     

Analyzing and understanding the robustness of bioprocesses

The robustness of bioprocesses is becoming increasingly important. The main driving forces of this development are, in particular, increasing demands on product purities as well as economic aspects. In general, bioprocesses exhibit extremely high complexity and variability. Biological systems often have a much higher intrinsic variability compared with chemical processes, which makes the development and characterization of robust processes tedious task. To predict and control robustness, a clear understanding of interactions between input and output variables is necessary. Robust bioprocesses can be realized, for example, by using advanced control strategies for the different unit operations. In this review, we discuss the different biological, technical, and mathematical tools for the analysis and control of bioprocess robustness.     

Biotechnological potential of inulin for bioprocesses

Inulin consists of linear chains of β-2,1-linked d-fructofuranose molecules terminated by a glucose residue through a sucrose-type linkage at the reducing end. In this review article, inulin and its applications in bioprocesses are overviewed. The tubers of many plants, such as Jerusalem artichoke, chicory, dahlia, and yacon contain a large amount of inulin. Inulin can be actively hydrolyzed by microbial inulinases to produce fructose, glucose and inulooligosaccharides (IOS). The fructose and glucose formed can be further transformed into ethanol, single-cell protein, single cell oil and other useful products by different microorganisms. IOS formed have many functions. Therefore, inulin can be widely used in food, feed, pharmaceutical, chemical and biofuels industries.     

Integrated bioprocesses

Integrated bioprocesses have been developed to optimise yield and cost-effectiveness of production of low and high molecular weight molecules. Low molecular weight products are removed from the cultivation medium with in situ extraction, in situ adsorption or crystallisation to avoid product inhibition. One-pot processes are being developed to replace two-stage reactions. Recent developments in the integrated purification of high molecular weight products focus mainly on the integration of solid/liquid separation and initial product recovery such as expanded bed adsorption or extraction in aqueous two-phase systems. Additionally, new approaches for a more efficient processing of inclusion bodies have been developed.     

Microbial engineering strategies to improve cell viability for biochemical production

Efficient production of biochemicals using engineered microbes as whole-cell biocatalysts requires robust cell viability. Robust viability leads to high productivity and improved bioprocesses by allowing repeated cell recycling. However, cell viability is negatively affected by a plethora of stresses, namely chemical toxicity and metabolic imbalances, primarily resulting from bio-synthesis pathways. Chemical toxicity is caused by substrates, intermediates, products, and/or by-products, and these compounds often interfere with important metabolic processes and damage cellular infrastructures such as cell membrane, leading to poor cell viability. Further, stresses on engineered cells are accentuated by metabolic imbalances, which are generated by heavy metabolic resource consumption due to enzyme overexpression, redistribution of metabolic fluxes, and impaired intracellular redox state by co-factor imbalance. To address these challenges, herein, we discuss a range of key microbial engineering strategies, substantiated by recent advances, to improve cell viability for commercially sustainable production of biochemicals from renewable resources.     

Greenhouse Gas and Energy Life Cycle Assessment of Pine Chemicals Derived from Crude Tall Oil and Their Substitutes

Pine chemicals are co‐products of papermaking that are upgraded into diverse products from inks to adhesives. They can also be utilized for energy purposes. This research investigates the carbon and energy life cycle assessment (LCA) of pine chemicals derived from crude tall oil (CTO). The study goals are to determine the cradle‐to‐gate carbon and energy footprint for CTO‐derived chemicals, compare CTO‐derived chemicals to their likely substitutes, and calculate the carbon and energy effects of shifting CTO resources from current chemical production to biodiesel production. The data collected represent 100% of the U.S. and 90% of the European CTO distillation industry for 2011. This analysis is the first industry‐level LCA of pine chemicals. The carbon footprint for CTO‐derived pine chemical products is 50% lower than the likely mix of alternative products, including hydrocarbon resins for rubber, ink, and adhesive, alkyl succinic anhydride for paper size, and heavy fuel oil for heat. Current and proposed European policies could result in CTO being classified as renewable biomass for energy production, creating incentive to convert CTO into fuel rather than chemicals. The differences in the carbon and energy footprints of utilizing CTO for biodiesel versus chemicals are not meaningful when comparing European CTO biodiesel, which displaces conventional diesel, to European CTO‐derived chemicals, which displace the previously discussed substitutes. Therefore, there is no additional carbon or energy benefit that accrues by diverting CTO from current chemical feedstock applications to use for biodiesel production in Europe.     

Synthesis of bioprocesses using physical properties data

The aim of this article is to illustrate and evaluate a synthesis procedure which has been extended to tackle bioprocesses. Physical property information is used to screen candidate units thereby reducing the size of the synthesis problem. In this way, only units which exploit large property differences between components in a stream are selected. This is important for bioprocesses because of the large number of components and wide range of unit operations which are available. The screening technique and bioprocess-unit-design methodologies have been incorporated within an implicit enumeration algorithm which was developed for chemical process synthesis and is implemented in Java programming language. An important advantage is the ability of the bioprocess synthesis software to generate a ranked list of flowsheets which may subsequently be analyzed in more detail. Two case studies are used to evaluate the bioprocess-synthesis technique. The first system involves a product which is secreted from the host organism. The second has significantly different characteristics in that the product is intracellular and forms inclusion bodies. The latter case study, in particular, is a large synthesis problem with 12 unit operations and 20 contaminant compounds. The results show that the synthesis methodology identifies a set of economically optimal flowsheets in a reasonable computational time which demonstrates its ability to deal with large synthesis problems. Using the synthesis methodology we can generate bioprocesses which are optimal in a system-wide, rather than unit-by-unit, sense.     

New developments in solid state fermentation: I-bioprocesses and products

The last decade has witnessed an unprecedented increase in interest in solid state fermentation (SSF) for the development of bioprocesses, such as bioremediation and biodegradation of hazardous compounds, biological detoxification of agro-industrial residues, biotransformation of crops and crop-residues for nutritional enrichment, biopulping, and production of value-added products, such as biologically active secondary metabolites, including antibiotics, alkaloids, plant growth factors, etc. enzymes, organic acids, biopesticides, including mycopesticides and bioherbicides, biosurfactants, biofuel, aroma compounds, etc. SSF systems, which during the previous two decades were termed as a ‘low-technology’ systems, appear to be a promising one for the production of value-added ‘low volume-high cost’ products such as biopharmaceuticals. SSF processes offer potential advantages in bioremediation and biological detoxification of hazardous and toxic compounds. With the advent of biotechnological innovations, mainly in the area of enzyme and fermentation technology, many new avenues have opened for the application of SSF. This review discusses more recent developments in the area of SSF leading to the developments of bioprocesses and products.     

Integrated product formation and recovery in fermentation.

Fermentation processes are hampered by a variety of problems originating from the accumulation of products in the fermenter. Integration of fermentation and a primary product separation step can accelerate the product formation, improve the product yield, and facilitate downstream processing. The advantages of integrated bioprocesses, however, are counteracted by the incompatibility of the subprocesses. Over the past few years, research in this field has been directed towards the development of engineering tools to reduce integration problems, to select a suitable approach, and to predict the feasibility of the integrated process. More fundamental knowledge about metabolic pathways, control mechanisms, and process dynamics is needed in order to optimally design integrated systems.     

Foaming: Consequences, prevention and destruction

This review examines the significance of foaming in bioprocesses, the mechanics of foam formation and destruction, and the methods of foam control and suppression. Emphasis is given to chemical antifoaming agents and characterization of their efficiencies. Criteria for selecting antifoaming agents are discussed.     

Extractive recovery of products from fermentation broths

Considerations of partition coefficients, selectivity, biocompatibility, and waste generation are important in selection of appropriate solvents to be used for extractive recovery of products from fermentation broths. Several selection criteria can be used based upon the nature of different species present in the broth. These criteria, along with examples of specific case studies, were presented. These serve not only in screening of useful solvents, but also in pointing to the specific modes of operation of recovery-coupled bioprocesses.     

Programmable bacterial catalysis - designing cells for biosynthesis of value-added compounds

Bacteria have long been used for the synthesis of a wide range of useful proteins and compounds. The developments of new bioprocesses and improvements of existing strategies for syntheses of valuable products in various bacterial cell hosts have their own challenges and limitations. The field of synthetic biology has combined knowledge from different science and engineering disciplines and facilitated the advancement of novel biological components which has inspired the design of targeted biosynthesis. Here we discuss recent advances in synthetic biology with relevance to biosynthesis in bacteria and the applications of computational algorithms and tools for manipulation of cellular components. Continuous improvements are necessary to keep up with increasing demands in terms of complexity, scale, and predictability of biosynthesis products.     

A scaled-down model for the translation of bacteriophage culture to manufacturing scale

Therapeutic bacteriophages are emerging as a potential alternative to antibiotics and synergistic treatment of antimicrobial-resistant infections. This is reflected by their use in an increasing number of recent clinical trials. Many more therapeutic bacteriophage is being investigated in preclinical research and due to the bespoke nature of these products with respect to their limited infection spectrum, translation to the clinic requires combined understanding of the biology underpinning the bioprocess and how this can be optimized and streamlined for efficient methods of scalable manufacture. Bacteriophage research is currently limited to laboratory scale studies ranging from 1–20 ml, emerging therapies include bacteriophage cocktails to increase the spectrum of infectivity and require multiple large-scale bioreactors (up to 50 L) containing different bacteriophage–bacterial host reactions. Scaling bioprocesses from the milliliter scale to multi-liter large-scale bioreactors is challenging in itself, but performing this for individual phage-host bioprocesses to facilitate reliable and robust manufacture of phage cocktails increases the complexity. This study used a full factorial design of experiments approach to explore key process input variables (temperature, time of infection, multiplicity of infection, agitation) for their influence on key process outputs (bacteriophage yield, infection kinetics) for two bacteriophage–bacterial host bioprocesses (T4 – Escherichia coli; Phage K – Staphylococcus aureus). The research aimed to determine common input variables that positively influence output yield and found that the temperature at the point of infection had the greatest influence on bacteriophage yield for both bioprocesses. The study also aimed to develop a scaled down shake-flask model to enable rapid optimization of bacteriophage batch bioprocessing and translate the bioprocess into a scale-up model with a 3 L working volume in stirred tank bioreactors. The optimization performed in the shake flask model achieved a 550-fold increase in bacteriophage yield and these improvements successfully translated to the large-scale cultures.     

Advantages of using thermophiles in biotechnological processes: expectations and reality

When thermophilic organisms were first considered for use in biotechnology, certain advantages were expected. The extraordinarily high reaction rates and insensitivity of processes to contaminations have not been experienced in practice, but over the last decade increasing interest has been shown in the possibility of deriving a wide variety of bioproducts from thermophiles. In addition to their high thermostability they also promise to have greater tolerance to organic solvents and a longer useful life. The possibility of recovering volatile products directly from a culture provides the opportunity to develop simplified, elegant bioprocesses. However, a series of engineering problems remain to be solved.     

Bioprocess engineering: now and beyond 2000

Abstract: Bioprocess engineering may be defined as the translation of life-science discoveries into practical products, processes, or systems capable of serving the needs of society. It is a critical link from discovery to commercialization. Current bioprocess engineering is primarily focused on biopharmaceutical products of high dollar value per gram such as erythropoietin or growth hormones. However, other products of current interest include ethanol, amino acids, organic acids, antibiotics, and specialty chemicals. Current challenges for increased use of bioprocesses for producing bulk and semi-bulk chemicals include both technical and infrastructural barriers. Technical barriers are easy to identify and at times can be overcome by engineering improvements or changes brought about radical developments in science (e.g. recombinant DNA). Infrastructural barriers, such as raw-material substitutions or educational limitations are more difficult to define and change. Recently the National Academy of Sciences examined barriers to bioprocess engineering and issued a report entitled: "Putting Biotechnology to Work: Bioprocess Engineering". A key recommendation was the establishment of a coordinated long-range plan of research, development, training and education in bioprocess engineering involving participation by industry, academe and the federal government. The report was the first national analysis devoted entirely to bioprocess engineering and covered new topics such as space bioprocess engineering. Other topics covered by the author include the current state of the US chemical industry and future directions in three promising areas of bioprocess engineering environmental bioprocess engineering, marine bioprocess engineering and microsystem bioprocess engineering.