Aromatic polyketide synthase type

If identical plant and microbial polyketides are indeed derived by common or closely related pathvwiys, it would appear that higher plant species can produce both types of synthases required for the formation of mode F and mode S-cyclised fused ring polyketides. The biosynthesis of aloesaponarin II by steptomycetes is known to involve an iterative type IIPKS and, by analogy with other fungal aromatic polyketide synthases, it is likely that a type I PKS is responsible for the formation of chrysophanol. However, at present little is known of the nature of PKSs responsible for the formation of fused ring polyketides in plants. 

Type II polyketide synthases, also referred to as bacterial aromatic polyketide synthases (25) are involved in the biosynthesis of a number of clinically important bacterial aromatic polyketides products exhibiting antitumor or antibiotic activity, such as doxorubicin and oxytetracycline. As mentioned, type II synthases are evolutionarily and structurally related to type II FASs, which occurr as heteromultimeric complexes. In contrast to type I synthases however, where multiple catalytic sites occur within a given subunit, the polypeptides associated with type II synthase complexes are typically monofimctional and dissociable 20,30). 

Acylation of peptides by aliphatic or aromatic carboxylic acids is followed by different routes. The respective carboxylic acids are supplied by linked ptolyke-tide synthases, either of the fatty acid or various polyketide synthase types, and introduced as either CoA esters or activated directly as adenylates. Several such activating systems have been characterized (see Section III.A.5). To initiate peptide synthesis with CoA esters, respective transferases arc required ... 

The polyketide synthases responsible for chain extension of cinnamoyl-CoA starter units leading to flavonoids and stilbenes, and of anthraniloyl-CoA leading to quinoline and acridine alkaloids (see page 377) do not fall into either of the above categories and have now been termed Type TTT PKSs. These enzymes differ from the other examples in that they are homodimeric proteins, they utilize coenzyme A esters rather than acyl carrier proteins, and they employ a single active site to perform a series of decarboxylation, condensation, cyclization, and aromatization reactions. 

Aloe (Aloe arborescens) is a medicinal plant rich in aromatic polyketides such as pharmaceutically important aloenin (a hexaketide pyrone), aloesin (a heptaketide chromone), and barbaloin (an octaketide anthrone) (Fig. 4a). Pentaketide chromone synthase (PCS) and octaketide synthase (OKS) are novel plant-specific type III PKSs, which were obtained from the aloe plant by RT-PCR cloning using degenerate oligonucleotide primers based on the conserved sequences of known CHS enzymes [30-33]. The deduced amino acid sequences of PCS and OKS are 91% identical (368/403), and show 50-60% identity to those of other CHS superfamily type III PKSs of plant origin OKS shares 60% identity (240/403) with CHS from... 

Abe I, Utsumi Y, Oguro S, Noguchi H (2004) The Hrst plant type III polyketide synthase catalyzing formation of aromatic heptaketide. FEBS Lett 562 171-176... 

Abe I, Takahashi Y, Noguchi H (2002) Enzymatic formation of an unnatural C6-C5 aromatic polyketide by plant type III polyketide synthases. Org Lett 4 3623-3626... 

Aromatic polyketides are structurally diverse, often polycyclic molecules that are derived from unreduced polyketone chains. This group of compounds is produced with the help of type II polyketide synthase (PKS), a complex of enzymes that catalyzes the iterative decarboxylative condensation of malonyl-CoA extender units with an acyl starter unit [70], The carbon framework of aromatic polyketides is further decorated with different functionalities, and carbohydrates are often one of them. Their presence has profound effects on physico-chemical and biological properties of aromatic polyketides. For example, anthracycline aglycones are stable and unpolar, while polyglycosylated anthracyclines are quite polar and often... 

Macrolides and polyethers such as erythromycin A (4), FK 506, rapamycin or avermectin A (5, Scheme 1) are products of modular type I polyketide-synthases. These compounds are distinguished by extraordinary structural diversity and complexity [1,2]. Because of their biological potency, members of this structural class as well as the aromatic polycyclic products of type II polyketide-synthases, tetracyclines and anthara-cyclines, e.g. adriamycin (6), became useful as pharmaceuticals (antibiotics, cytostatics, immunosuppressives) [1,2],... 

Chalcone synthase (CHS), the first plant natural product polyketide synthase (PKS) to be characterized at the molecular level (39), catalyzes the condensation of 4-coumaroyl-CoA with three molecules of malonyl-CoA to afford naringenin chalcone, a precursor of the major classes of plant flavonoids. The cloning of a novel type III pentaketide chromone synthase (PCS) from aloe (Aloe arborescens, Liliaceae) rich in aromatic polyketides, especially quinones such as aloe-emodin and emodin, resulted in... 

Meuter G, Hutchinson CR. Daunorubicin Type il polyketide synthase enzymes DpsA and DpsB determine neither the choice of starter unit nor the cyclization pattern of aromatic polyketides. ] Am Chem Soc 1995 117 5899-5900. 

Figure 8 Typical aromatic antibiotics made by (A) bacterial type II iterative polyketide synthases and (B) (vingal type 1 iterative polyketide synthases- Norsolorinic acid is the precursor of aflatoxin...

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