This review is an updated and expanded version of the three prior reviews that were published in this journal in 1997, 2003, and 2007. In the case of all approved therapeutic agents, the time frame has been extended to cover the 30 years from January 1, 1981, to December 31, 2010, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2010 for all approved antitumor drugs worldwide. We have continued to utilize our secondary subdivision of a “natural product mimic” or “NM” to join the original primary divisions and have added a new designation, “natural product botanical” or “NB”, to cover those botanical “defined mixtures” that have now been recognized as drug entities by the FDA and similar organizations. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules, 131, or 74...

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Natural Products As Sources of New Drugs over the 30 Years from 1981 to 2010

The use of biocatalysis for industrial synthetic chemistry is on the verge of significant growth. Biocatalytic processes can now be carried out in organic solvents as well as aqueous environments, so that apolar organic compounds as well as water-soluble compounds can be modified selectively and efficiently with enzymes and biocatalytically active cells. As the use of biocatalysis for industrial chemical synthesis becomes easier, several chemical companies have begun to increase significantly the number and sophistication of the biocatalytic processes used in their synthesis operations.

Industrial biocatalysis today and tomorrow

Over the past ten years, scientific and technological advances have established biocatalysis as a practical and environmentally friendly alternative to traditional metallo- and organocatalysis in chemical synthesis, both in the laboratory and on an industrial scale. Key advances in DNA sequencing and gene synthesis are at the base of tremendous progress in tailoring biocatalysts by protein engineering and design, and the ability to reorganize enzymes into new biosynthetic pathways. To highlight these achievements, here we discuss applications of protein-engineered biocatalysts ranging from commodity chemicals to advanced pharmaceutical intermediates that use enzyme catalysis as a key step.

Engineering the third wave of biocatalysis

Immobilization is often the key to optimizing the operational performance of an enzyme in industrial processes, particularly for use in non-aqueous media. Different methods for the immobilization of enzymes are critically reviewed. The methods are divided into three main categories, viz. (i) binding to a prefabricated support (carrier), (ii) entrapment in organic or inorganic polymer matrices, and (iii) cross-linking of enzyme molecules. Emphasis is placed on relatively recent developments, such as the use of novel supports, e.g., mesoporous silicas, hydrogels, and smart polymers, novel entrapment methods and cross-linked enzyme aggregates (CLEAs).

http://largens.com/biochemlab/peroxidase2.pdf

Enzyme immobilization: The quest for optimum performance

Metal–organic frameworks (MOFs), also known as porous coordination polymers (PCPs), synthesized by assembling metal ions with organic ligands have recently emerged as a new class of crystalline porous materials. The amenability to design as well as fine-tunable and uniform pore structures makes them promising materials for a variety of applications. Controllable integration of MOFs and functional materials is leading to the creation of new multifunctional composites/hybrids, which exhibit new properties that are superior to those of the individual components through the collective behavior of the functional units. This is a rapidly developing interdisciplinary research area. This review provides an overview of the significant advances in the development of diverse MOF composites reported till now with special emphases on the synergistic effects and applications of the composites. The most widely used and successful strategies for composite synthesis are also presented.

Metal–organic framework composites

Biocatalysis has emerged as an important tool in the industrial synthesis of bulk chemicals, pharmaceutical and agrochemical intermediates, active pharmaceuticals, and food ingredients. However, the number and diversity of the applications are modest, perhaps in part because of perceived or real limitations of biocatalysts, such as limited enzyme availability, substrate scope, and operational stability. Recent scientific breakthroughs in genomics, directed enzyme evolution, and the exploitation of biodiversity should help to overcome these limitations. As a result, we expect many new industrial applications of biocatalysis to be realized, from single-step enzymatic conversions to customized multistep microbial synthesis by means of metabolic pathway engineering.

https://science.sciencemag.org/content/sci/299/5613/1694.full.pdf

Dispelling the myths--biocatalysis in industrial synthesis.

Many Pseudomonads are able to use linear alkanes as sole carbon and energy source. The genetics and enzymology of alkane metabolism have been investigated in depth forPseudomonas oleovorans, which is able to oxidize C5-C12 n-alkanes by virtue of two gene regions, localized on the OCT-plasmid. The so-calledalk-genes have been cloned in pLAFR1, and were subsequent analyzed using minicell expression experiments, DNA sequencing and deletion analysis. This has led to the identification and characterization of thealkBFGHJKL andalkST genes which encode all proteins necessary to convert alkanes to the corresponding acyl-CoA derivatives. These then enter the β-oxidation-cycle, and can be utilized as carbon- and energy sources. Medium (C6-C12)- or long-chain (C13-C20) n-alkanes can be utilized by many strains, some of which have been partially characterized. The alkane-oxidizing enzymes used by some of these strains (e.g. twoP. aeruginosa strains, aP. denitrificans strain and a marinePseudomonas sp.) appear to be closely related to those encoded by the OCT-plasmid.

Marcel Wubbolts

Papers

Industrial biocatalysis today and tomorrow

Dispelling the myths--biocatalysis in industrial synthesis.

Genetics of alkane oxidation by Pseudomonas oleovorans

Metabolic engineering for microbial production of aromatic amino acids and derived compounds.

Industrial Biocatalysis Today and Tomorrow