Protein Acylation is a General Regulatory Mechanism in Biosynthetic Pathway of Acyl-CoA-Derived Natural Products

被引：32

作者：

Xu, Jun-Yu ^{[1
,2
,3
]}

Xu, Ya ^{[3
]}

Xu, Zhen ^{[3
]}

Zhai, Lin-Hui ^{[2
]}

Ye, Yang ^{[2
]}

Zhao, Yingming ^{[2
,4
]}

Chu, Xiaohe ^{[1
]}

Tan, Minjia ^{[2
]}

Ye, Bang-Ce ^{[1
,3
]}

机构：

[1] Zhejiang Univ Technol, Coll Pharmaceut Sci, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Hangzhou 310014, Zhejiang, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China

[3] East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Lab Biosyst & Microanal, Shanghai 200237, Peoples R China

[4] Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA

来源：

CELL CHEMICAL BIOLOGY | 2018年 / 25卷 / 08期

基金：

中国国家自然科学基金;

关键词：

S-ADENOSYLMETHIONINE SYNTHETASE; LYSINE ACETYLATION; ESCHERICHIA-COLI; SACCHAROPOLYSPORA-ERYTHRAEA; QUANTITATIVE PROTEOMICS; BACTERIAL PRODIGININES; METABOLIC-REGULATION; POLYKETIDE SYNTHASE; STRAIN IMPROVEMENT; SYSTEMS BIOLOGY;

D O I：

10.1016/j.chembiol.2018.05.005

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Coenzyme A (CoA) esters of short fatty acids (acyl-CoAs) function as key precursors for the biosynthesis of various natural products and the dominant donors for lysine acylation. Herein, we investigated the functional interplay between beneficial and adverse effects of acyl-CoA supplements on the production of acyl-CoA-derived natural products in microorganisms by using erythromycin-biosynthesized Saccharopolyspora erythraea as a model: accumulation of propionyl-CoA benefited erythromycin biosynthesis, but lysine propionylation inhibited the activities of important enzymes involved in biosynthetic pathways of erythromycin. The results showed that the overexpression of NAD(+)-dependent deacylase could circumvent the inhibitory effects of high acyl-CoA concentrations. In addition, we demonstrated the similar lysine acylation mechanism in other acyl-CoA-derived natural product biosynthesis, such as malonyl-CoA-derived alkaloid and butyryl-CoA-derived bioalcohol. These observations systematically uncovered the important role of protein acylation on interaction between the accumulation of high concentrations of acyl-CoAs and the efficiency of their use in metabolic pathways.

引用

页码：984 / +

页数：18

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