Naphthoate synthase

Formation of the coenzyme A ester of the aliphatic carboxyl group of o-succinylbenzoic acid (38) appears to activate the methylene proton sufficiently to permit attack at the aromatic carboxyl group (Fig. 6.7). 2-Carboxy-4-oxotetra-lone (COT) (43) and/or l,4-dihydroxy-2-naphthoic acid (DHNA) (40) are likely intermediates for later stages of synthesis. The enzymatic conversion to DHNA with naphthoate synthase (which consists of OSB CoA synthetase and DHNA synthetase) requires ATP, Mg ", and coenzyme A. 1,4-Dihy-droxy-2-naphthoic acid (40) is a precursor of vitamin K2 (35) and menaquinones (such as 44) (Inouye and Leistner,... 

Fig. 144. Biosynthesis of naphthoquinone and anthraquinone derivatives from chorismic acid 1 2-Succinylbenzoate synthase 2 2-succinylbenzoate Co A ligase, naphthoate synthase 3 l,4-dihydroxy-2-naphtho-ate polyprenyltransferase...

It is very likely that a similar Type I polyketide synthase constructs the naphthoate fragment of azinomycin B. This will be a very interesting enzyme to study, since it will need to perform an unprecedented three regioselective reduction reactions, as well as controlling the polyketide chain length and directing its cycliza-tion. 

Figure 3.10 Pathway to the naphthoate fragment (i) condensation hy a polyketide synthase (ii) ketone reduction, aldol cychzation, aromatization (iii) hydroxylation, possibly by cytochrome P450 (iv) methylation using S-adenosylmethionine.

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