A Proteomic Survey of Nonribosomal Peptide and Polyketide Biosynthesis in Actinobacteria

被引：34

作者：

Chen, Yunqiu ^{[1
,2
]}

Ntai, Ioanna ^{[1
,2
]}

Ju, Kou-San ^{[3
]}

Unger, Michelle ^{[1
,2
]}

Zamdborg, Leonid ^{[5
]}

Robinson, Sarah J. ^{[1
,2
]}

Doroghazi, James R. ^{[3
]}

Labeda, David P. ^{[6
]}

Metcalf, William W. ^{[3
,4
]}

Kelleher, Neil L. ^{[1
,2
,3
]}

机构：

[1] Northwestern Univ, Dept Chem, Evanston, IL 60208 USA

[2] Northwestern Univ, Chem Life Proc Inst, Evanston, IL 60208 USA

[3] Univ Illinois, Inst Genom Biol, Urbana, IL 61801 USA

[4] Univ Illinois, Dept Microbiol, Urbana, IL 61801 USA

[5] Univ Illinois, Coll Med, Urbana, IL 61801 USA

[6] Agr Res Serv, USDA, Midw Area, Natl Ctr Agr Utilizat Res,Bacterial Foodborne Pat, Peoria, IL 61604 USA

来源：

JOURNAL OF PROTEOME RESEARCH | 2012年 / 11卷 / 01期

基金：

美国国家科学基金会;

关键词：

nonribosomal peptide; polyketide; natural product biosynthesis; actinobacteria; de novo sequencing; Fourier-Transform Mass Spectrometry; NATURAL-PRODUCT; PREDICTION; DISCOVERY; SOFTWARE; SEQUENCE;

D O I：

10.1021/pr2009115

中图分类号：

Q5 [生物化学];

学科分类号：

070307 [化学生物学];

摘要：

Actinobacteria such as streptomycetes are renowned for their ability to produce bioactive natural products including nonribosomal peptides (NRPs) and polyketides (PKs). The advent of genome sequencing has revealed an even larger genetic repertoire for secondary metabolism with most of the small molecule products of these gene clusters still unknown. Here, we employed a "protein-first" method called PrISM (Proteomic Investigation of Secondary Metabolism) to screen 26 unsequenced actinomycetes using mass spectrometry-based proteomics for the targeted detection of expressed nonribosomal peptide synthetases or polyketide synthases. Improvements to the original PrISM screening approach (Nat. Biotechnol. 2009, 27, 951-956), for example, improved de novo peptide sequencing, have enabled the discovery of 10 NRPS/PKS gene clusters from 6 strains. Taking advantage of the concurrence of biosynthetic enzymes and the secondary metabolites they generate, two natural products were associated with their previously "orphan" gene clusters. This work has demonstrated the feasibility of a proteomics-based strategy for use in screening for NRP/PK production in actinomycetes (often >8 Mbp, high GC genomes) versus the bacilli (2-4 Mbp genomes) used previously.

引用

页码：85 / 94

页数：10

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