Natural product enzyme cofactors

Natural product molecules are biosynthesized by a sequence of reactions which, with very few exceptions, are catalysed by enzymes. Enzymes are protein molecules which facilitate chemical modification of substrates by virtue of their specific binding properties conferred by the particular combination of functional groups in the constituent amino acids. In many cases, a suitable cofactor, e.g. NAD+, PLP, HSCoA (see below), as well as the substrate, may also be bound to participate in the transformation. Although enzymes catalyse some fairly elaborate and sometimes unexpected changes, it is generally possible to account for the reactions using sound chemical principles and mechanisms. As we explore the pathways to a wide variety of natural products, the reactions will generally be... 

Isoprenoids are one of the largest classes of natural products that comprise at least 35,000 reported members (48). Many of these compounds play crucial roles in human metabolism as hormones, vitamins (vitamins A, D, E and K), quinine-type cofactors of respiratory chain enzymes (ubiquinone), membrane constituents, and functionally important side chains of signal cascade proteins (Fig. 11). Chlorophyll (17, Fig. 2) and heme a (18) have isoprenoid side chains. 

Pichia stipitis. P. stipitis is the most effective natural yeast for the conversion of xylose to ethanol. This yeast species shares many characteristics with its close relative, C. shehatae. Toivola et al. [90] performed a systemic screening program with type strains of some 200 yeast species and identified P. stipitis as one of the yeast species that produces ethanol from xylose. There are many studies that have explored the property of this yeast in relation to its oxygen requirement, ethanol tolerance, enzyme cofactor s balance, etc. According to the reported literature [91,92], ethanol production from xylose by P stipitis exhibits the following characteristics ... 

The tetrapyrroles are a group of natural products which include the haems (e.g. haem hl), the chlorophylls (e.g. chlorophyll a 2) and the corrinoids (e.g. coenzyme Bi2 4), see Scheme 1 [1 -6]. In addition to these well-known and widespread enzymic cofactors, other tetrapyrroles are used in more restricted cases. 

Vitamin B12 (cyanocobalamin) 3 is, in fact, not a natural product as the cyanide ligand to the cobalt ion is added during the isolation procedure. Coenzyme B12 (adenosylcobalamin) 4 and methylcobalamin 5 are the true final products of the biosynthetic pathway. Coenzyme 0,2 is the cofactor for a number of enzymic rearrangement reactions, such as that catalysed by methylmalonyl CoA mutase, and methylcobalamin is the cofactor for certain methyl transfer reactions, including the synthesis of methionine. A number of anaerobic bacteria produce related corrinoids in which the dimethylbenzimidazole moiety of the cobalamins (3 - 5) is replaced by other groups which may or may not act as ligands to the cobalt ion, such as adenine orp-cresol [12]. 

Pyrazino[2,3-d/]pyrimidines are known as pteridines , because the first examples of the ring system, as natural products, were found in pigments, like xanthopterin (yellow), in the wings of bntterflies (Lepidoptera). The pteridine ring system has subsequently been found in coenzymes that use tetrahydrofolic acid (derived from the vitamin folic acid), and in the cofactor of the oxomolybdoenzymes and comparable tungsten enzymes. 

The use of isolated enzymes to form or cleave P-O bonds is an important application of biocatalysts. Restriction endonucleases, (deoxy)ribonucleases, DNA/ RNA-ligases, DNA-RNA-polymerases, reverse transcriptases etc. are central to modern molecular biology(1). Enzyme catalyzed phosphoryl transfer reactions have also found important applications in synthetic organic chemistry. In particular, the development of convenient cofactor regeneration systems has made possible the practical scale synthesis of carbohydrates, nucleoside phosphates, nucleoside phosphate sugars and other natural products and their analogs. This chapter gives an overview of this field of research. 

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