Lobophorins (LOBs) belong to a large family of spirotetronate
antibiotics with antibacterial and antitumor activities. In this study,
we demonstrated the function of LobP1, a P450 monooxygenase encoded in
the LOB biosynthetic gene cluster, by in vivo deletion and
in vitro biochemical assays. The disruption of lobP1 led
to the isolation of three new LOBs derivatives (3‒5)
and three known ones (6‒8) without the hydroxyl group
at C-32. LobP1 was shown to have relatively broad substrate scope.
Determining the kinetic parameters of LobP1 towards different substrates
revealed that LobP1 preferred substrate with a nitrosugar. The major
product LOB E (6) from the ∆lobP1 mutant displayed
better cytotoxic activities against several cancer cell lines than LOB
B, the C-32 hydroxylated counterpart.
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