LITMIR.BIZ

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yield isomeric forms."/> 6 Ligases Formation of C–C, C–S, C–O, and C–N bonds by condensation reactions coupled to ATP cleavage, e.g.

      By international agreement, the catalytic reaction is assigned and identified by a group of four‐digit number according to the enzyme classification system. For example, the enzyme catalyzes the transfer of a phosphoryl group from ATP to D‐glucose is named as ATP:glucose phosphotransferase. The enzyme is classified as

Transferase	Main class 2
Phosphotransferase	Subclass 7
Using a hydroxyl group as acceptor	Subgroup 1
D‐Glucose as the phosphoryl‐group acceptor	The serial number 1

The serial number of the last digit of an enzyme is identified by the first three entrees. Therefore, the Enzyme Commission number (E.C. number) of this enzyme is 2.7.11 denoted as E.C. 2.7.1.1. However, a trivial name, hexokinase, is more commonly used for this enzyme.

1.6 Enzyme and Green Chemistry

      Green chemistry, also known as sustainable chemistry, is an emerging field in chemistry and is highly advocated by global researchers recently. Green chemistry emphasizes the design of products and chemical processes that reduce or eliminate the use or production of hazardous substances [31]. Whereas sustainability has been defined as “meeting the needs of the present generation without compromising the ability of future generations to meet their needs.” Therefore, green chemistry can also be thought as a critical tool in attaining sustainability by developing new technologies in all kinds of applications such as food and drink, medicine, energy, biofuels, plastics, and nanotechnology. Also, the long‐term entanglement of the “three E’s” problems – Energy, Economy, and Environment – could be solved by applying the 12 principles of green chemistry to assure a sustainable society in the future.

The 12 principles of green chemistry listed in Table 1.5 [31, 32] were proposed by Paul T. Anastas and John C. Warner in 1998 that has become the index to implement the green/sustainable chemistry. How chemical synthesis catalyzed by enzyme is related with green chemistry? As mentioned before, the substrate specificity of enzyme greatly reduces the formation of byproducts, thus greatly increases the atom economy of the reaction. Enzymes are biodegradable natural material that does not threat human health and make environmental pollution. The regioselectivity, particularly, the stereoselectivity of enzymes can be used to design and produce safe drugs of no toxicity and without side‐effects by raising the enantiomeric excess (%ee) value or yield. The reaction conditions for enzyme‐catalyzed reaction are mild, usually at low temperature and under atmospheric pressure, and the solvent used is innocuous water that makes an energy efficient and clean synthetic process. The substrate for enzyme can be either renewable or nonrenewable source that gives the enzyme reaction wide and flexible applications. Various specificities of enzyme show great advantage in avoiding the use of blocking groups, protection/deprotection, or temporary modification of physical/chemical processes, thus reduce the synthetic steps for a final target product to a minimum that saves a lot of chemical reagents and generates minimal wastes. Immobilized enzyme‐catalyzed reaction is most feasible to couple an online analytical technique to perform real‐time monitoring and control of hazardous substances [33, 34].

Table 1.5 Twelve principles of green chemistry.

      Source: Based on Anstas and Warner [31]; Hill et al. [32].

Prevention: It is better to prevent waste than to treat or clean up waste after it has been created.Atom Economy: Synthetic methods should be designed to maximize the incorporation of all materials used in the process into the final product.Less Hazardous Chemical Syntheses: Wherever practicable, synthetic methods should be designed to use and generate substances that possess little or no toxicity to human health and the environment.Designing Safer Chemicals: Chemical products should be designed to affect their desired function while minimizing their toxicity.Safer Solvents and Auxiliaries: The use of auxiliary substances (e.g. solvents, separation agents) should be made unnecessary wherever possible and innocuous when used.Design for Energy Efficiency: Energy requirements of chemical processes should be recognized for their environmental and economic impacts and should be minimized. If possible, synthetic methods should be conducted at ambient temperature and pressure.Use of Renewable Feedstocks: A raw material or feedstock should be renewable rather than depleting whenever technically and economically practicable.Reduce Derivatives: Unnecessary derivatization (use of blocking groups, protection/deprotection, and temporary modification of physical/chemical processes) should be minimized or avoided, if possible, because such steps require additional reagents and can generate waste.Catalysis: Catalytic reagents (as selective as possible) are superior to stoichiometric reagents.Design for Degradation: Chemical products should be designed so that at the end of their function they break down into innocuous degradation products and do not persist in the environment.Real‐time Analysis for Pollution Prevention: Analytical methodologies need to be further developed to allow for real‐time, in‐process monitoring, and control prior to the formation of hazardous substances.Inherently Safer Chemistry for Accident Prevention: Substances and the form of a substance used in a chemical process should be chosen to minimize the potential for chemical accidents, including releases, explosions, and fires.

Probably, the greatest disadvantage of free‐enzyme catalyzed reaction for green chemistry is only one time usage of the expensive purified enzyme due to the difficulty of enzyme recovery. To overcome this drawback, the enzyme‐catalyzed reaction can be performed by using whole microbial cell. However, the use of whole cell catalyzed reaction can be considered convenient against the free enzyme reaction under three situations: (i) as the enzyme is intracellular; (ii) as the enzyme needs a cofactor to carry out the catalysis; and (iii) the formation of product through a multienzymatic processes. The other strategy is to perform the enzyme reaction with immobilized enzyme that can be recovered and reused many times. However, the maintenance of activity for the recovered enzyme is a big challenge in present technology. Nevertheless, this is probably the fundamental approach for enzyme‐catalyzed reaction to fulfill green chemistry.

      To encourage and propel the implementation of green chemistry, the Presidential Green Chemistry Challenge Award was established by the United States government in 1996. The following are several award winners that can be used as models in green chemistry by using enzyme and related microbe for production of chemicals [35].

      The winner of year 2011: Production of Basic Chemicals from Renewable Feedstocks at Lower Cost

      Genomatica has developed a microbe using sophisticated genetic engineering to make 1,4‐butanediol (BDO) (a high‐volume chemical building block used to make many common polymers, such as spandex) by fermenting sugars. When produced at commercial scale, Genomatica’s Bio‐BDO will be less expensive, require about 60% less energy, and produce 70% less carbon dioxide emissions than BDO made from natural gas.

      1.7 The Winner of Year 2010: Greener Manufacturing of Sitagliptin Enabled by an Evolved Transaminase

      Merck and Codexis have developed a second‐generation green synthesis of sitagliptin, the active ingredient in Januvia, a treatment for type 2 diabetes. This collaboration has led to an enzymatic process with transaminase that reduces waste, improves yield and safety, and eliminates the need for a metal catalyst. Early research suggests that the new biocatalysts will be useful in manufacturing

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