Abstract:
BACKGROUND:Griseoviridin (GV) and viridogrisein (VG, also referred as etamycin), both biosynthesized by a distinct 105 kb biosynthetic gene cluster (BGC) in Streptomyces griseoviridis NRRL 2427, are a pair of synergistic streptogramin antibiotics and very important in treating infections of many multi-drug resistant microorganisms. Three transporter genes, sgvT1-T3 have been discovered within the 105 kb GV/VG BGC, but the function of these efflux transporters have not been identified. RESULTS:In the present study, we have identified the different roles of these three transporters, SgvT1, SgvT2 and SgvT3. SgvT1 is a major facilitator superfamily (MFS) transporter whereas SgvT2 appears to serve as the sole ATP-binding cassette (ABC) transporter within the GV/VG BGC. Both proteins are necessary for efficient GV/VG biosynthesis although SgvT1 plays an especially critical role by averting undesired intracellular GV/VG accumulation during biosynthesis. SgvT3 is an alternative MFS-based transporter that appears to serve as a compensatory transporter in GV/VG biosynthesis. We also have identified the γ-butyrolactone (GBL) signaling pathway as a central regulator of sgvT1-T3 expression. Above all, overexpression of sgvT1 and sgvT2 enhances transmembrane transport leading to steady production of GV/VG in titers ≈ 3-fold greater than seen for the wild-type producer and without any notable disturbances to GV/VG biosynthetic gene expression or antibiotic control. CONCLUSIONS:Our results shows that SgvT1-T2 are essential and useful in GV/VG biosynthesis and our effort highlight a new and effective strategy by which to better exploit streptogramin-based natural products of which GV and VG are prime examples with clinical potential.
journal_name
Microb Cell Factjournal_title
Microbial cell factoriesauthors
Xie Y,Ma J,Qin X,Li Q,Ju Jdoi
10.1186/s12934-017-0792-8subject
Has Abstractpub_date
2017-10-25 00:00:00pages
177issue
1issn
1475-2859pii
10.1186/s12934-017-0792-8journal_volume
16pub_type
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journal_title:Microbial cell factories
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journal_title:Microbial cell factories
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journal_title:Microbial cell factories
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journal_title:Microbial cell factories
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journal_title:Microbial cell factories
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更新日期:2017-11-21 00:00:00
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journal_title:Microbial cell factories
pub_type: 杂志文章
doi:10.1186/1475-2859-7-11
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journal_title:Microbial cell factories
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journal_title:Microbial cell factories
pub_type: 杂志文章
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