“…The formation of the spiroketal is facilitated by several avoenzymes, which are known to be mechanistically versatile. 10,11,13,[17][18][19][20][21][22][23][24][25] Accordingly, generation of 4a mainly depends on the group A avoprotein monooxygenase (FPMO) GrhO5, 15 which is assisted by avoprotein oxidase GrhO1. 16 The subsequent conversion of the [6,6]-spiroketal-containing 4a into 5a via oxygenation and succeeding decarboxylative ring contraction depends on a second group A FPMO, GrhO6, while further downstream steps require further investigation and presumably proceed via dihydro-7,8-dideoxygriseorhodin C (6a) to the mature rubromycins such as 1 and 2.…”