TY - JOUR
T1 - LeTetR positively regulates 3-hydroxylation of the antifungal HSAF and its analogs in lysobacter enzymogenes OH11
AU - Yu, Lingjun
AU - Khetrapal, Vimmy
AU - Liu, Fengquan
AU - Du, Liangcheng
N1 - Funding Information:
Funding: This research was funded in part by the University of Nebraska Collaboration Initiative Seed Grant, and the Nebraska Public Power District through the Nebraska Center for Energy Sciences Research at the University of Nebraska-Lincoln.
Funding Information:
Acknowledgments: We thank Jiangsu Academy of Agricultural Sciences for the postdoctoral fellowship to L.Y.
PY - 2020/5
Y1 - 2020/5
N2 - The biocontrol agent Lysobacter enzymogenes OH11 produces several structurally distinct antibiotic compounds, including the antifungal HSAF (Heat Stable Antifungal Factor) and alteramides, along with their 3-dehydroxyl precursors (3-deOH). We previously showed that the 3-hydroxylation is the final step of the biosynthesis and is also a key structural moiety for the antifungal activity. However, the procedure through which OH11 regulates the 3-hydroxylation is still not clear. In OH11, the gene orf3232 was predicted to encode a TetR regulator (LeTetR) with unknown function. Here, we deleted orf3232 and found that the LeTetR mutant produced very little HSAF and alteramides, while the 3-deOH compounds were not significantly affected. The production of HSAF and alteramides was restored in orf3232-complemented mutant. qRT-PCR showed that the deletion of orf3232 impaired the transcription of a putative fatty acid hydroxylase gene, orf2195, but did not directly affect the expression of the HSAF biosynthetic gene cluster (hsaf). When an enzyme extract from E. coli expressing the fatty acid hydroxylase gene, hsaf-orf7, was added to the LeTetR mutant, the production of HSAF and alteramides increased by 13–14 fold. This study revealed a rare function of the TetR family regulator, which positively controls the final step of the antifungal biosynthesis and thus controls the antifungal activity of the biocontrol agent.
AB - The biocontrol agent Lysobacter enzymogenes OH11 produces several structurally distinct antibiotic compounds, including the antifungal HSAF (Heat Stable Antifungal Factor) and alteramides, along with their 3-dehydroxyl precursors (3-deOH). We previously showed that the 3-hydroxylation is the final step of the biosynthesis and is also a key structural moiety for the antifungal activity. However, the procedure through which OH11 regulates the 3-hydroxylation is still not clear. In OH11, the gene orf3232 was predicted to encode a TetR regulator (LeTetR) with unknown function. Here, we deleted orf3232 and found that the LeTetR mutant produced very little HSAF and alteramides, while the 3-deOH compounds were not significantly affected. The production of HSAF and alteramides was restored in orf3232-complemented mutant. qRT-PCR showed that the deletion of orf3232 impaired the transcription of a putative fatty acid hydroxylase gene, orf2195, but did not directly affect the expression of the HSAF biosynthetic gene cluster (hsaf). When an enzyme extract from E. coli expressing the fatty acid hydroxylase gene, hsaf-orf7, was added to the LeTetR mutant, the production of HSAF and alteramides increased by 13–14 fold. This study revealed a rare function of the TetR family regulator, which positively controls the final step of the antifungal biosynthesis and thus controls the antifungal activity of the biocontrol agent.
KW - Alteramides
KW - HSAF
KW - Lysobacter enzymogenes
KW - Natural product
KW - Regulation
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U2 - 10.3390/molecules25102286
DO - 10.3390/molecules25102286
M3 - Article
C2 - 32414039
AN - SCOPUS:85084882515
VL - 25
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 10
M1 - 2286
ER -