Applied Chemistry, Vol.8, No.2, 474-477, October, 2004
An Unique Iterative Type I PKS, Neocarzinostatin Naphthoate Synthase: Analysis and swapping of domain with AviM
An enediyne antibiotic, Neocarzinostatin (NCS), produced by Streptomyces carzinostaticus is a potent anticancer antibiotic and is structurally constituted with warhead diene, the naphthoic acid moiety and a sugar moiety. The NNS was heterologously expressed in Streptomyces hosts and the product was isolated and identified as 2-hydroxy-5-methyl-1-naphthoic acid (major) along with minor 2, 7-dihydroxy-5-methyl-1-naphthoic acid. Taking into an account the isolation of bicyclic aromatic compound and the monocyclic compound from the bacterial PKSs, which in turn have similar domain organizations, the chain length factor can be analyzed by swapping of domains to observe the expected hybrid compound. The KS and KS/ACP domains from bicyclic aromatic compound producer Streptomyces carzinostaticus and monocyclic aromatic compound producer Streptomyces viridochromogenes Tu 57 have been swapped to establish the factor.