Biosynthetic methods

Kiick KL (2007) Biosynthetic methods for the production of advanced protein-based materials. Polym Rev 47 1-7... 

Full exploitation of cascade catalysis and multi-step conversions in concert will require the development of novel, mutually compatible, organic and biosynthetic methods and procedures. Eventually, a full integration of organic synthesis and biosynthesis can be envisaged. 

Selected entries from Methods in Enzymology [vol, page(s)] Determination of FMN and FAD by fluorescence titration with apoflavodoxin, 66, 217 purification of flavin-adenine dinucleotide and coenzyme A on p-acetoxymercurianiline-agarose, 66, 221 a convenient biosynthetic method for the preparation of radioactive flavin nucleotides using Clostridium kluyveri, 66, 227 isolation, chemical synthesis, and properties of roseoflavin, 66, 235 isolation, synthesis, and properties of 8-hydroxyflavins, 66, 241 structure, properties and determination of covalently bound flavins, 66, 253 a two-step chemical synthesis of lumiflavin, 66, 265 syntheses of 5-deazaflavins, 66, 267 preparation, characterization, and coenzymic properties of 5-carba-5-deaza and 1-... 

Esters are usually prepared by esterification of carboxylic acids with alcohols. Industrial procedures depend on the physical properties of the esters concerned. Biosynthetic methods may be applied to produce natural esters for flavor purposes [24]. 

Preparation of Insulins. Until the early 1980s insulin for therapeutic purposes was produced almost exclusively by extraction from beef and pork pancreases. Between 100 and 400 mg of insulin can be obtained from each kg of pancreatic tissue, and it has been estimated that there would be sufficient supplies of animal insulin to meet the requirements of diabetic patients into the twenty-first century (2). Through modem purification procedures animal insulins can be prepared in essentially pure form, which eliminates the possibility of developing antibodies against impurities in the insulin preparations. However, patients treated with purified insulins still develop antibodies to insulin, suggesting that differences in the primary structures of these insulins might stimulate antibody production. Therefore, enzymatic and biosynthetic methods have been developed for the preparation of therapeutic insulin identical to human insulin. 

Biosynthetic methods to produce the MurD substrate, UMA, are not suitable for making the large quantities required for a high-throughput screen. Methods for chemically synthesizing the substrate were therefore developed and scaled up so as to provide the multigram quantities required for the screen and its development. 

The use of biosynthetic methods to stereoselectively acylate iV-hydroxymethyl substituents on some bicyclic /3-lactams has been mentioned in Section 2.04.8.1 <2003TA3805>. 

This is a safe, low cost, and more convenient approach as it does not involve special instrumentation, poisonous intermediates, and the growing rate can also be easily controlled. The utility of this process is underlined by the fact that even after continuous exposure to the toxic metal ions, the fungus readily grows and transforms the toxic conditions to nontoxic by reducing Cd to CdS without the use of any external source of sulfur. Another important, potential benefit of the process described is the fact that the semiconductor CdS nanoparticles, which are quite stable in solution, are synthesized extracellularly in large quantities. This is therefore, a very important advantage over other biosynthetic methods where the nanoparticles are entrapped within the cell matrix in limited quantity whereby an additional processing is required to release them from the matrix. 

The use of renewable feedstocks for creating alternative synthetic routes to chemicals of major industrial importance is exemplified by the biosynthetic method for producing hydroquinone, benzoquinone, catechol, and ci.v-ci.v-muconic acid from glucose by means of a genetically altered... 

Structure elucidation of antibiotics and preparation of new substances using biosynthetic methods 88YGK490. 

New approaches to source novel compounds from untapped areas of biodiversity coupled with the technical advances in analytical techniques (such as microcoil NMR and linked LC-MS-NMR) have removed many of the difficulties when using natural products in screening campaigns. As the chemical space occupied by natural products is both more varied and more drug-like than that of combinatorial chemical collections, synthetic and biosynthetic methods are being developed to produce screening libraries of natural product-like compounds. A renaissance of drug discovery inspired by natural products can be predicted.2... 

Biosynthetic methods for its production as natural flavor material have been developed [12a], [18]. 

Historically important not used or not now important as an antibacterial drug. b Report on therapeutic efficacy of crude penicillin. c Produced by biosynthetic methods not utilized until 1953. dUsed primarily or exclusively in animals. 

In principle, biosynthetic methods can provide structural variants that are inaccessible or very difficultly accessible by chemical methods on the other hand, except where incorporation of a wide variety of precursors is possible these methods do not now provide a means for directly making pre-selected changes in structure. Enzymatic or microbiological transformation of antibiotics is a related approach that in principle can bring about selective and specific structural changes. Although this method was used with success in the steroid field, it has not yet provided... 

Given a wealth of natural chemical scaffolds for improved drug design, our ability to generate novel pharmaceuticals requires increased understanding of the biosynthetic processes that may lead to their discovery and production. Polyketide and nonribosomal peptide assembly offers enormous potential for development of combinatorial biosynthetic methods. The structural complexity of these natural products often prohibits practical chemical synthesis, which underscores the need for alternative means of accessing them in usable quantities. Research in this area requires in-depth knowledge of chemical,... 

S. Anthonycahill, C.J. Noren, P.G. Schultz, P. G. Biosynthetic method for introducing unnatural amino-acids site-specifically into proteins, Methods Enzymol. 1991,... 

It is possible to introduce new redox groups into proteins using chemical and/ or biosynthetic methods. Attachment of mthenium to specific histidine residues on various electron transfer proteins has provided a method for the characterization of intramolecular electron transfer processes in proteins (77, 78). Studies of intramolecular electron transfer in ruthenated proteins are described in more detail in Section IV. 

Anthracyclines are large and chemically labile molecules, which makes their synthetic modification challenging, hi biosynthetic methods, reactions are performed mostly in neutral aqueous solutions at moderate temperatures. Enzymatic reactions are highly specific for the position as well as the stereoisomer modified Hkewise, chiral products are exclusively of one stereoisomer. Particularly in vivo, in Hving organisms, enzymatic reactions can be combined to perform several modifications in one process, or, indeed, to build the entire molecule from simple precursors. One of the strengths of biosynthetic methods is also their main weakness only modifications for which an enzyme exists can be performed. 

There are, of course, many difficulties to overcome but signs that this can be achieved are encouraging. Earlier problems of accessibility are being eased with the displacement of biosynthetic methods of preparation by total chemical synthesis and the latter is also making available prostaglandin analogues... 

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