Assessing oxazole bioisosteres as mutasynthons on the rhizoxin assembly line.

Chain armor against tumor cells: The oxazole side chain in the antimitotic agent rhizoxin S2 (1) was successfully replaced through mutasynthesis by using an engineered mutant impaired in heterocyclization. Incorporation of 12 non-natural surrogates into fully processed rhizoxin analogues revealed a remarkable substrate flexibility of the PKS-NRPS hybrid.