Polyketides pentaketides

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, Morita H, Sano Y, Noguchi H (2005) A plant Type III polyketide synthase that produces pentaketide chromone. J Am Chem Soc 127 1362-1363... 

Morita H, Kondo S, Abe T, Noguchi H, Sugio S, Abe I, Kohno T (2006) Crystallization and preliminary crystallographic analysis of a novel plant type III polyketide synthase that produces pentaketide chromone. Acta Crystallograph Sect F Struct Biol Cryst Commun 62 899-901... 

Several important chalcone synthase-related PKSs have recently been discovered in bacteria. 21 RppA is a Type III PKS that synthesizes 1,3,6,8-tetrahydroxynaph-thalene (THN) from five malonyl-CoAs in Streptomyces griseusf RppA specifically cyclizes the pentaketide intermediate via two intramolecnlar condensations to yield the bicyclic THN. The crystal stractnre of a closely related THN synthase (THNS) from S. coelicolor was recently determined, uncovering the presence of a second active-site cysteine that stablizes the growing polyketide and prevents aberrant cyclization of the highly reactive pentaketide. ... 

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... 

Penicillic acid provides an example of a simple tetra-ketide whose aromatic ring is cleaved and cyclized, as shown by experiments with [l,2- C2]-acetate (Fig. 4). On the other hand, the pentaketide citrinin is the result of the cyclization of a linear polyketide chain wherein... 

Acetate is also a precursor of several groups of alkaloids in the form of a polyketide chain that interacts with an unknown nitrogen source (as in the terpene alkaloids). Examples of acetate-derived alkaloids are coniine—the toxic principle of Conium maculatum, pinidine—from several Pinus species, and the naphthy-lisoquinoline alkaloids (e.g., ancistrocladine)—showing antimalarial and anti-HIV activity. The latter alkaloids are apparently derived from the oxidative coupling of two pentaketide units. Huperzine A, currently in clinical trials for the treatment of Alzheimer s disease and isolated from the club moss (Serrata huperzia), is derived from a polyacetate precursor (Fig. 46). 

An exercise in the folding of the polyketide chain to make a simple pentaketide. 

The biosynthetic reduction of the polyketide chain may prevent the formation of aromatic products. Instead, several lactones are formed. For example, a series of bio-active pentaketide metabolites containing a ten-membered ring have been isolated. These include the diplodialides e.g. diplodialide A, 4.73) from Diplodia pinea, the pyrenolides e.g. pyrenolide A, 4.74) from Pyrenophora teres and the cephalosporolides e.g. cephalosporolide B, 4.75) from Cephalosporium aphidi-cola. An unusual dimeric pentaketide, thiobiscephalosporolide A (in which the two lactones are held together by a sulfur), has also been obtained from... 

Figure 1 Hypothetical pentaketide biosynthetic system, which illustrates the enzymatic logic of type I modular polyketide synthases (PKSs) and the catalytic role of acyl transferase (AT) domains. Each AT domain selects substrates from the cellular pool and tethers them as thioesters to acyl carrier protein (ACP) domains. In a typical PKS module, the AT and ACP domains are present in all modules. The ketosynthase (KS) domain is present in all chain extension modules. The dehydratase (DH), enoyl reductase (ER), and ketoreductase (KR) domains are optional domains. The final thioesterase (TE) domain catalyzes the release of the product from the PKS.

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