PMID- 27018252
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20170802
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 473
IP  - 1
DP  - 2016 Apr 22
TI  - Identification of an unusual type II thioesterase in the dithiolopyrrolone 
      antibiotics biosynthetic pathway.
PG  - 329-335
LID - S0006-291X(16)30418-1 [pii]
LID - 10.1016/j.bbrc.2016.03.105 [doi]
AB  - Dithiolopyrrolone group antibiotics characterized by an electronically unique 
      dithiolopyrrolone heterobicyclic core are known for their antibacterial, 
      antifungal, insecticidal and antitumor activities. Recently the biosynthetic gene 
      clusters for two dithiolopyrrolone compounds, holomycin and thiomarinol, have 
      been identified respectively in different bacterial species. Here, we report a 
      novel dithiolopyrrolone biosynthetic gene cluster (aut) isolated from 
      Streptomyces thioluteus DSM 40027 which produces two pyrrothine derivatives, 
      aureothricin and thiolutin. By comparison with other characterized 
      dithiolopyrrolone clusters, eight genes in the aut cluster were verified to be 
      responsible for the assembly of dithiolopyrrolone core. The aut cluster was 
      further confirmed by heterologous expression and in-frame gene deletion 
      experiments. Intriguingly, we found that the heterogenetic thioesterase HlmK 
      derived from the holomycin (hlm) gene cluster in Streptomyces clavuligerus 
      significantly improved heterologous biosynthesis of dithiolopyrrolones in 
      Streptomyces albus through coexpression with the aut cluster. In the previous 
      studies, HlmK was considered invalid because it has a Ser to Gly point mutation 
      within the canonical Ser-His-Asp catalytic triad of thioesterases. However, gene 
      inactivation and complementation experiments in our study unequivocally 
      demonstrated that HlmK is an active distinctive type II thioesterase that plays a 
      beneficial role in dithiolopyrrolone biosynthesis.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Zhai, Ying
AU  - Zhai Y
AD  - National Key Laboratory of Agricultural Microbiology, College of Life Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China.
FAU - Bai, Silei
AU  - Bai S
AD  - National Key Laboratory of Agricultural Microbiology, College of Life Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China.
FAU - Liu, Jingjing
AU  - Liu J
AD  - National Key Laboratory of Agricultural Microbiology, College of Life Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China.
FAU - Yang, Liyuan
AU  - Yang L
AD  - National Key Laboratory of Agricultural Microbiology, College of Life Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China.
FAU - Han, Li
AU  - Han L
AD  - Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, 
      Northeastern University, Shenyang 110819, China.
FAU - Huang, Xueshi
AU  - Huang X
AD  - Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, 
      Northeastern University, Shenyang 110819, China.
FAU - He, Jing
AU  - He J
AD  - National Key Laboratory of Agricultural Microbiology, College of Life Science and 
      Technology, Huazhong Agricultural University, Wuhan 430070, China. Electronic 
      address: hejingjj@mail.hzau.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160324
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Pyrroles)
RN  - 0 (Sulfhydryl Compounds)
RN  - 0KX00L19Q2 (aureothricin)
RN  - EC 3.1.- (Esterases)
RN  - EC 3.1.2.- (Thiolester Hydrolases)
SB  - IM
MH  - Anti-Bacterial Agents/chemistry
MH  - Bacterial Proteins/*biosynthesis/genetics/metabolism
MH  - Biosynthetic Pathways
MH  - Catalytic Domain
MH  - Cloning, Molecular
MH  - Computational Biology
MH  - Esterases/genetics/*metabolism
MH  - Gene Deletion
MH  - Gene Expression Regulation, Bacterial
MH  - Multigene Family
MH  - Phylogeny
MH  - Pyrroles/*chemistry
MH  - Streptomyces/*enzymology/genetics
MH  - Sulfhydryl Compounds/*chemistry
MH  - Thiolester Hydrolases/*biosynthesis/chemistry
OTO - NOTNLM
OT  - Aureothricin
OT  - Biosynthetic gene cluster
OT  - Dithiolopyrrolone
OT  - Heterologous expression
OT  - In-frame gene deletion
OT  - Type II thioesterase
EDAT- 2016/03/29 06:00
MHDA- 2016/09/23 06:00
CRDT- 2016/03/29 06:00
PHST- 2016/03/07 00:00 [received]
PHST- 2016/03/22 00:00 [accepted]
PHST- 2016/03/29 06:00 [entrez]
PHST- 2016/03/29 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
AID - S0006-291X(16)30418-1 [pii]
AID - 10.1016/j.bbrc.2016.03.105 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2016 Apr 22;473(1):329-335. doi: 
      10.1016/j.bbrc.2016.03.105. Epub 2016 Mar 24.