posted on 2021-11-04, 19:04authored byJiayu Liu, Yangyang Zhao, Zheng Qing Fu, Fengquan Liu
Self-resistance genes are deployed
by many microbial producers
of bioactive natural products to avoid self-toxicity. Myxin, a di-N-oxide phenazine produced by Lysobacter
antibioticus OH13, is toxic to many microorganisms
and tumor cells. Here, we uncovered a self-defense strategy featuring
the antibiotic biosynthesis monooxygenase (ABM) family protein LaPhzX
for myxin degradation. The gene LaPhzX is located
in the myxin biosynthetic gene cluster (LaPhz), and
its deletion resulted in bacterial mutants that are more sensitive
to myxin. In addition, the LaPhzX mutants showed
increased myxin accumulation and reduction of its derivative, compound 4, compared to the wild-type strain. Meanwhile, in vitro biochemical
assays demonstrated that LaPhzX significantly degraded myxin in the
presence of nicotinamide adenine dinucleotide phosphate (NADPH), nicotinamide
adenine dinucleotide (NADH), flavin mononucleotide (FMN), and flavin
adenine dinucleotide (FAD). In addition, heterologous expression of LaPhzX in Xanthomonas oryzae pv. oryzae and Escherichia coli increased their resistance to myxin. Overall, our work illustrates
a monooxygenase-mediated self-resistance mechanism for phenazine antibiotic
biosynthesis.