Applied Bioengineering

Innovations and Future Directions

Toshiomi Yoshida, Sang Yup Lee, Jens Nielsen, Gregory Stephanopoulos

• Publisher: Wiley-VCH
• Year: 2017
• Print ISBN: 9783527340750
• eBook ISBN: 9783527800605
• Edition: 1
• Topic: Biological Sciences
• Subtopic: Biotechnology
• Index: Biological Sciences

A comprehensive overview of the topic, highlighting recent developments, ongoing research trends and future directions.
Experts from Europe, Asia and the US cover five core areas of imminent importance to the food, feed, pharmaceutical and water treatment industries in terms of sustainable and innovative processing and production. In the field of enzyme engineering, they summarize historic developments and provide an overview of molecular enzyme engineering, while also discussing key principles of microbial process engineering, including chapters on process development and control. Further sections deal with animal and plant cell culture engineering. The final section of the book deals with environmental topics and highlights the application of bioengineering principles in waste treatment and the recovery of valuable resources.
With its cutting-edge visions, extensive discussions and unique perspectives, this is a ready reference for biotechnologists, bioengineers, bioengineers, biotechnological institutes, and environmental chemists.

1
Introduction

Toshiomi Yoshida

1.1 Introduction

The European Federation of Biotechnology proposed a definition of biotechnology as “The integration of natural science and organisms, cells, parts thereof and molecular analogs for products and services.” The Concise Oxford English Dictionary states “biotechnology is the exploitation of biological processes for industrial and other purposes especially the genetic manipulation of microorganisms for the production of antibiotics, hormone, and so on” [1].

Biochemical engineering has developed as a branch of chemical engineering, and deals with the design and construction of unit processes that involve biological molecules or organisms. Biochemical engineering is often taught as a supplementary option to students of chemical engineering or biological engineering courses because of the overlap in the curriculum and similarities in problem-solving techniques used in both professions. Its contribution is widely found in the food, feed, pharmaceutical, and biotechnological industries, and in water treatment plants.

Biological engineering or bioengineering is the application of the concepts, principles, and methods of biology to solve real-world problems using engineering methodologies and also its traditional sensitivity to the cost advantage and practicality. In this context, while traditional engineering applies physical and mathematical sciences to analyze, design, and manufacture inanimate tools, structures, and processes, biological engineering primarily utilizes knowledge of molecular biology to study, investigate, and develop applications of living organisms. In summary, biological engineers principally focus on applying engineering principles and the knowledge of molecular biology to study and enhance biological systems for varied applications.

Referring to the above review and brief discussion, it is proposed to have a section titled “Applied Bioengineering” be included in the Wiley Biotechnology Series. This section will deal with recent progress in all subjects closely related to “engineering and technologies” in the field of biotechnology; widening the coverage beyond conventional biochemical engineering and bioprocess engineering to include other biology-based engineering disciplines. The topics involved were selected specifically from the perspective of practical applications.

The volume “Applied Bioengineering” comprises five topics: enzyme technology, microbial process engineering, plant cell culture, animal cell culture, and environmental bioengineering. Each topic is figured in several chapters, though with more chapters pertaining to environmental bioengineering. This field has seen an increase in active research as mentioned below because of growing awareness and concern about conservation, remediation, and improvement of the environment.

The later part of this chapter provides a brief overview on the developments in bioengineering, referring to recent highly cited research.

1.2 Enzyme Technology

Recently, several attempts have been made to screen organic-solvent-tolerant enzymes from various microorganisms [2]. The ligninolytic oxidoreductases are being improved utilizing protein engineering by the application of different “omics” technologies. Enzymatic delignification will soon come into practical use in pulp mills [3]. Enzyme stabilization has been attempted using various approaches such as protein engineering, chemical modification, and immobilization [4].

Microbial glucose oxidase has garnered considerable interest because of its wide applications in chemical, pharmaceutical, food, beverage, clinical chemistry, biotechnology, and other industries. Novel applications of glucose oxidase in biosensors have further increased its demand [5]. Numerous oxidative biotransformation studies have demonstrated that enzymes have diverse characteristics and wide range of potential, and established applications [6]. Multienzymatic cascade reactions used in the asymmetric synthesis of chiral alcohols, amines, and amino acids, as well as for C–C bond formation, have been extensively studied [7].

1.3 Microbial Process Engineering

1.3.1 Bioreactor Development

Stirred-tank bioreactors are used in a large variety of bioprocesses because of their high rates of mass and heat transfer and excellent mixing. Theoretical predictions of the volumetric mass transfer coefficient have been recently proposed, and different criteria for bioreactor scale-up have been reported [8].

Miniaturized bioreactor (MBR) systems have made great advances both in function and in performance. The dissolved oxygen transfer performance of submilliliter microbioreactors and 1–10 ml mini-bioreactors has been well examined. MBRs have achieved considerably high k_La values and offer flexible instrumentation and functionality comparable to that of production systems at high-throughput screening volumes; furthermore, the superior integration of these bioreactors with automated fluid handling systems demonstrates that they allow efficient scale-up [9].

The pharmaceutical and biotechnology industries face constant pressure to reduce development costs and accelerate process development. A small scale bioreactor system enabling multiple reactions in parallel (n ≥ 20) with automated sampling would provide significant improvement in development timelines. State-of-the-art equipment that facilitates high-throughput process developments includes shake flasks, microfluidic reactors, microtiter plates, and small-scale stirred reactors [10].

An expert panel organized by the M³C Working Group of the European Section of Biochemical Engineering Science (ESBES) reviewed the prevailing methods of monitoring of MBRs and identified the need for further development [11]. Their recommendations includes combining online analytics such as chromatography or mass spectrometry with bioreactors, preferably using noninvasive sensors such as optical or electronic ones. The sensors to be used online in these bioreactors should be selected on the basis of three criteria: (i) detection limits in relation to analytes, (ii) stability in relation to the testing period, and (iii) the possibility for miniaturization to the volume ranges and dimensions of the microfluidic system applied in the bioreactors. In addition, mathematical models based on soft sensor principles should be exploited to reduce the number of sensors.

1.3.2 Measurement and Monitoring

Biosensors for detection of cellobiose, lactose, and glucose based on various cellobiose dehydrogenases from different fungal producers, which differ with respect to their substrate specificity, optimum pH, electron transfer efficiency, and surface-binding affinity; therefore, promising a wide range of new applications [12].

Infrared sensors are ideal tools for bioprocess monitoring, because they are noninvasive, of no-time-delay, and harmless on the bioprocess itself, and furthermore, simultaneous analyses of several components are possible. Therefore, directly monitoring of substrates, products, metabolites, and the biomass itself is possible [13]. The panel of the M³C Working Group of ESBES recommended the use of soft sensors in bioprocess engineering [14]. In the Food and Drug Administration's (FDA) proposed and promoted process analytical technology (PAT) initiative, intending to collaborate with industry to promote the integration of new manufacturing technologies with pharmaceutical production [15]. The program aimed to design, develop, and operate processes consistently ensuring a predefined quality at the end of the manufacturing process [15]. An advanced monitoring and control system has been developed, based on different inline, online and at-line measurements for substrates and products. Observation of cell viability by inline measurement of radio frequency impedance and online determination of intracellular recombinant target protein using the reporter protein T-sapphire green fluorescent protein (GFP) could allow real-time monitoring of critical process states [16].

1.3.3 Modeling and Control

Stoichiometric models of cell metabolism have been developed with the use of information about reaction stoichiometry embedded in metabolic networks and the assumption of a pseudo-steady state. Stoichiometric models have been used to estimate the metabolic flux distribution under given circumstances in the cell at some given moment (metabolic flux analysis) and to predict it on the basis of some optimality hypothesis (flux balance analysis). Mechanistic models based on deterministic principles, recently, have been interested in substantially. Gernaey et al. [17] highlighted the utility of models with respect to the selection of variables required for t...

Table of contents

• Cover
• Related Titles
• Title Page
• Copyright
• Table of Contents
• List of Contributors
• 1: Introduction
• Part I: Enzyme Technology
• Part II: Microbial Process Engineering
• Part III: Plant Cell Culture and Engineering
• Part IV: Animal Cell Cultures
• Part V: Environmental Bioengineering
• Index
• End User License Agreement