Abstract:
:Malonyl coenzyme A (malonyl-CoA) and methylmalonyl-CoA are the most common extender units for the biosynthesis of fatty acids and polyketides in Streptomyces, an industrially important producer of polyketides. Carboxylation of acetyl- and propionyl-CoAs is an essential source of malonyl- and methylmalonyl-CoAs; therefore, acyl-CoA carboxylases (ACCases) play key roles in primary and secondary metabolism. The regulation of the expression of ACCases in Streptomyces spp. has not been investigated previously. We characterized a TetR family transcriptional repressor, AccR, that mediates intracellular acetyl-, propionyl-, methylcrotonyl-, malonyl-, and methylmalonyl-CoA levels by controlling the transcription of genes that encode the main ACCase and enzymes associated with branched-chain amino acid metabolism in S. avermitilis AccR bound to a 16-nucleotide palindromic binding motif (GTTAA-N6-TTAAC) in promoter regions and repressed the transcription of the accD1A1-hmgL-fadE4 operon, echA8, echA9, and fadE2, which are involved in the production and assimilation of acetyl- and propionyl-CoAs. Methylcrotonyl-, propionyl-, and acetyl-CoAs acted as effectors to release AccR from its target DNA, resulting in enhanced transcription of target genes by derepression. The affinity of methylcrotonyl- and propionyl-CoAs to AccR was stronger than that of acetyl-CoA. Deletion of accR resulted in increased concentrations of short-chain acyl-CoAs (acetyl-, propionyl-, malonyl-, and methylmalonyl-CoAs), leading to enhanced avermectin production. Avermectin production was increased by 14.5% in an accR deletion mutant of the industrial high-yield strain S. avermitilis A8. Our findings clarify the regulatory mechanisms that maintain the homeostasis of short-chain acyl-CoAs in StreptomycesIMPORTANCE Acyl-CoA carboxylases play key roles in primary and secondary metabolism. However, the regulation of ACCase genes transcription in Streptomyces spp. remains unclear. Here, we demonstrated that AccR responded to intracellular acetyl-, propionyl-, and methylcrotonyl-CoA availability and mediated transcription of the genes related to production and assimilation of these compounds in S. avermitilis When intracellular concentrations of these compounds are low, AccR binds to target genes and represses their transcription, resulting in low production of malonyl- and methylmalonyl-CoAs. When intracellular acetyl-, propionyl-, and methylcrotonyl-CoA concentrations are high, these compounds bind to AccR to dissociate AccR from target DNA, promoting the conversion of these compounds to malonyl- and methylmalonyl-CoAs. This investigation revealed how AccR coordinates short-chain acyl-CoA homeostasis in Streptomyces.
journal_name
Appl Environ Microbioljournal_title
Applied and environmental microbiologyauthors
Lyu M,Cheng Y,Han X,Wen Y,Song Y,Li J,Chen Zdoi
10.1128/AEM.00508-20subject
Has Abstractpub_date
2020-06-02 00:00:00issue
12eissn
0099-2240issn
1098-5336pii
AEM.00508-20journal_volume
86pub_type
杂志文章abstract::The concentration of 2-aminoethylphosphonic acid has been measured in seven genera of rumen ciliate protozoa. Expressed as milligrams per gram of total nitrogen, 2-aminoethylphosphonic acid concentrations ranged from 17.2 in Ophryoscolex spp. to 72.4 in Eremoplastron spp. ...
journal_title:Applied and environmental microbiology
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doi:10.1128/AEM.46.4.951-953.1983
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doi:10.1128/AEM.61.3.1110-1115.1995
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pub_type: 杂志文章,评审
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更新日期:2017-01-17 00:00:00
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journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.65.9.4163-4170.1999
更新日期:1999-09-01 00:00:00
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更新日期:2001-05-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2005-08-01 00:00:00
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journal_title:Applied and environmental microbiology
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journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.56.4.1079-1086.1990
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journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.63.2.474-481.1997
更新日期:1997-02-01 00:00:00
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journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.45.4.1306-1309.1983
更新日期:1983-04-01 00:00:00
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journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.64.6.2026-2031.1998
更新日期:1998-06-01 00:00:00
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journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.65.3.903-909.1999
更新日期:1999-03-01 00:00:00
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journal_title:Applied and environmental microbiology
pub_type: 杂志文章
doi:10.1128/AEM.33.5.1097-1104.1977
更新日期:1977-05-01 00:00:00