Biocatalysis for Green Chemistry and Chemical Process Development

Junhua (Alex) Tao, Romas Joseph Kazlauskas, Junhua (Alex) Tao, Romas Joseph Kazlauskas

• Publisher: Wiley
• Year: 2011
• Print ISBN: 9780470437780
• eBook ISBN: 9781118028292
• Edition: 1
• Topic: Technology & Engineering
• Subtopic: Environmental Management
• Index: Technology & Engineering

This book describes recent progress in enzyme-driven green syntheses of industrially important molecules. The first three introductory chapters overview recent technological advances in enzymes and cell-based transformations, and green chemistry metrics for synthetic efficiency. The remaining chapters are directed to case studies in biotechnological production of pharmaceuticals (small molecules, natural products and biologics), flavors, fragrance and cosmetics, fine chemicals, value-added chemicals from glucose and biomass, and polymeric materials.

The book is aimed to facilitate the industrial applications of this powerful and emerging green technology, and catalyze the advancement of the technology itself.

Part I

INTRODUCTION CHAPTERS

Chapter 1

Biotechnology Tools for Green Synthesis: Enzymes, Metabolic Pathways, and their Improvement by Engineering

Romas J. Kazlauskas

Department of Biochemistry, Molecular Biology and Biophysics and The Biotechnology Institute, University of Minnesota , Saint Paul, Minnesota

Byung-Gee Kim

Department of Chemical and Biological Engineering, Seoul National University, Seoul, Korea

1.1 Introduction

Green chemistry is the design of products and processes that eliminate or reduce waste, toxic, and hazardous materials. Green chemistry is not a cleanup approach, but a prevention approach. Preventing problems is inevitably easier and less expensive than contending with difficulties after they occur.

The risk associated with a chemical depends both on how dangerous it is (hazard) and on one's contact with it (exposure) (Figure 1.1). In the past, governments and industry focused on reducing risk by minimizing exposure. Rules limit the exposure of workers to hazardous chemicals and the release of these chemicals into the environment. This approach is expensive; it is difficult to establish a safe level of hazardous chemicals, and currently, only a small fraction of the chemicals manufactured are regulated.

Figure 1.1 The risk associated with a chemical depends on both how dangerous it is (hazard) and one's contact with it (exposure). In the past, the focus was on minimizing exposure by rules that limit the amounts of hazardous chemicals in air and water. The green chemistry approach is to eliminate or reduce hazardous materials. This change requires redesigning of synthetic approaches.

The green chemistry approach focuses on reducing risk by reducing or eliminating the hazard. Hazardous materials are eliminated by, for example, replacing them with nonhazardous ones. Hazardous materials are eliminated also by increasing the yield of a reaction, as higher yield eliminates some of the waste from that reaction. In addition, higher yield allows any preceding reactions to be carried out on a smaller scale, thus eliminating some of the waste from these steps as well. This prevention approach saves money, as fewer raw materials are needed and the cost of treatment of waste is reduced.

Reducing costs and being environmentally friendly are goals that everyone agrees on. Why has this not been done before? One reason is that environmental costs were ignored in the early days of the chemical industry. Now that more of the cleanup cost falls on the manufacturer, there is a big financial incentive to be greener. Another reason is that chemists in research and design laboratories did not view environmental hazards as their problems. It was something to be fixed later in the scale-up stage. The green chemistry approach changes this thinking. By thinking about hazards and environmental consequences at the research and design stage, many problems are prevented and do not need a fix later. The principles of green chemistry outlined by Anastas and Warner [1] provide specific guidelines for what to look for at the research and design stage to make a greener process. These principles are discussed below in the context of biocatalysis.

The first use of biochemical reactions for organic synthesis was probably in 1858, when Louis Pasteur resolved tartaric acid by using a microorganism to destroy one enantiomer [2]. In spite of this early demonstration, chemists have used biocatalysis only sporadically. Chemists gradually recognized the potential of biochemical reactions, but there were both practical and conceptual hurdles. Practical problems were how to get the enzymes and how to stabilize them. The conceptual problems were beliefs that enzymes accept only a narrow range of biochemical intermediates as substrates, and that enzymes are too complex to consider engineering them for key properties like stability, stereoselectivity, substrate range, and even reaction type. The recent advances in biotechnology have solved many of the practical problems, and the increased understanding of biochemical structures and mechanisms has made biocatalysts more understandable to chemists. This chapter surveys the state of the art for engineering biocatalysts for chemistry applications. If you find an enzyme that catalyzes your desired reaction, regardless of how poor the enzyme is, it is highly likely that it can be engineered into an enzyme suitable for industrial and large-scale use.

1.2 The Natural Fit of Biocatalysis with Green Chemistry

Biotechnology methods fit naturally to the goals and principles of green chemistry. Green chemistry, or sustainable chemistry, seeks to integrate industrial manufacturing practice with the natural world. This natural world is the biological world, where sustainability and recycling are integral parts. Use of the biological methods for industrial manufacturing is an excellent starting point to create a green process. In some cases, biotechnology tools, unlike chemical tools, are even edible. Baker's yeast, used to make bread, also catalyzes the reduction of various carbonyl compounds. Lipases are the most commonly used enzymes for biocatalysis. These enzymes are also eaten in multigram amounts by patients with pancreatic insufficiency and in smaller amounts when food-grade lipases are used in the manufacture of cheese.

Although the “bio” part of biocatalysis makes it environmentally friendly, it is the “catalysis” part that provides the green chemistry advantage. Catalysis, in place of reagents, converts many substrate molecules to products and eliminates the need for stoichiometric reagents. Catalysis is fast, so the reaction may not need to be heated. This saves energy and may eliminate side reactions that occur at higher temperatures. Catalysis is selective, eliminating the need to add and remove protective groups or use auxiliaries to control reactivity. Catalysis can enable complex and otherwise difficult reactions. This ability can eliminate steps and simplify syntheses.

The 12 principles of green chemistry outline the design goals for synthesis. Making progress toward any one of these goals will make a synthesis greener; progress toward several goals is of course better. Table 1.1 lists some suggestions on how biocatalysis can help a synthesis toward these goals.

Table 1.1 How Biocatalysis Follows the Twelve Principles of Green Chemistry

Prevent waste

The high selectivity of enzymes and their ability to carry out difficult chemical reactions eliminate synthesis steps and the associated waste in multistep reactions. Reagents and solvents for eliminated steps are not needed; higher yield and selectivity in the remaining steps also eliminate waste. Biocatalysis usually uses water as the solvent, which eliminates organic solvent waste

Design safer chemicals and products

Biocatalysts are typically used only for manufacture and are not the product themselves. In some cases, a biocatalyst can be a product, such as an enzyme-based drain cleaner that replaces a drain cleaner based on a strong acid or base. Biocatalysis can enable the manufacture of new products, such as biodegradable polyesters, which is not practical to manufacture chemically

Design less hazardous chemical syntheses

Eliminating hazardous steps or replacing hazardous reagents with biocatalysts makes the manufacturing process safer

Use renewable feedstock

Biocatalysts are typically manufactured by growing microorganisms that secrete the biocatalysts. In other cases, the whole cells can be used as the catalysts. The feedstock to grow microorganisms are sugars and amino acids, which are renewable

Use catalysts, not stoichiometric reagents

Biocatalysts are highly efficient catalysts, that is, each enzyme molecule converts thousands to millions of substrate molecules to product. Thus, reactions are fast and the turnover number is high

Avoid chemical derivatives

The high selectivity of enzymes usually eliminates the need for protective groups and for resolutions involving chemical derivatives

Maximize atom economy

The high selectivity of enzymes and their ability to carry out difficult chemical reactions allow most of the starting material (including all reagents) atoms to be converted to the product. Eliminating synthesis steps, reagents, and derivatives reduces the number of atoms of the starting materials needed

Use safer solvents and reaction conditions

Biocatalysis typically uses water as the solvent, neutral pH, and room temperature. If needed for substrate solubility or faster reaction, biocatalysis can tolerate a wide range of reaction conditions, including organic solvents

Increase energy efficiency

Because biocatalysts are fast catalysts, one does not need to heat a reaction, thus saving energy. One also rarely needs to cool a reaction, which also requires energy, since the reaction rate can be reduced by adding less catalyst. The selectivity of biocatalysts is high, so there is no need to reduce the temperature to increase selectivity as there is with chemical reagents and catalysts

Design for degradation

Biocatalysts are biodegradable; some catalysts (e.g., baker's yeast and food-grade proteases) are even edible

Analyze in real time to prevent pollution

No special advantage of bi...

Table of contents

• Cover
• Title Page
• Copyright
• Preface
• Contributors
• Part I: Introduction Chapters
• Part II.: Application and Case Studies—Pharmaceuticals and Fine Chemicals
• Part III.: Application and Case Studies—Flavor & Fragrance, Agrochemicals and Fine Chemicals
• Part IV.: Application and Case Studies—polymers and renewable chemicals
• Index