Orsellinate synthase

A similar stereochemical outcome to that observed for 6-MSA was found using orsellinate synthase isolated from Penicillium cyclopium [58]. The hydrogens retained at C-3 and C-5 of orsellinic acid (66, R=OH) are from opposite prochiral sites in malonate. This contrasts with a previous study [59] on... 

Cell-free systems capable of in vitro synthesis of 6-methylsalicylic acid (6-MS A) and a related tetraketide, orsellinic acid, were developed long before the advent of recombinant DNA technologies in the field of natural product biosynthesis [113-115] (Fig. 5). Since then, the biosynthetic mechanisms and molecular recognition features of 6-methylsalicylic acid synthase (6-MSAS) have been extensively studied. 6-MSAS initiates synthesis with an acetyl group derived from acetyl Co A, extends the polyketide chain to a tetraketide via three decar-boxylative condensations of malonyl CoA-derived extender units, and uses NADPH to specifically reduce one of resulting carbonyls to a hydroxyl group. In its natural producer, Penicillium patulum, the product, 6-MSA is subsequently glycosylated to form the antibiotic patulin [116]. 

Similar stereochemical studies have also been conducted on the orsellinic acid synthase from Penicillium cyclopium, a multisubunit enzyme composed of a 130 kDa protein [129, 130]. The catalytic cycle of this PKS is identical to the 6-MSAS cycle, except that it lacks any ketoreduction or dehydration reactions. Unlike 6-MSAS, enolizations occurring during orsellinic acid biosynthesis are not stereospecific. 

The tetraketide orsellinic acid 1 is the simplest tetraketide, which requires no reductions during its biosynthesis. One of the first discovered fungal PKS, orsellinic acid synthase (OSAS)... 

The calicheamidn-specific orsellinic acid moiety and other snbstituent groups are produced via unique iterative type 1 polyketide synthases, with at least 20 genes in the calicheamicin biosynthetic gene clnster including those for the two... 

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