PMID- 33824341
OWN - NLM
STAT- MEDLINE
DCOM- 20210414
LR  - 20230106
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Apr 6
TI  - Biochemical and structural characterization of the BioZ enzyme engaged in 
      bacterial biotin synthesis pathway.
PG  - 2056
LID - 10.1038/s41467-021-22360-4 [doi]
LID - 2056
AB  - Biotin is an essential micro-nutrient across the three domains of life. The 
      paradigm earlier step of biotin synthesis denotes "BioC-BioH" pathway in 
      Escherichia coli. Here we report that BioZ bypasses the canonical route to begin 
      biotin synthesis. In addition to its origin of Rhizobiales, protein phylogeny 
      infers that BioZ is domesticated to gain an atypical role of beta-ketoacyl-ACP 
      synthase III. Genetic and biochemical characterization demonstrates that BioZ 
      catalyzes the condensation of glutaryl-CoA (or ACP) with malonyl-ACP to give 
      5'-keto-pimeloyl ACP. This intermediate proceeds via type II fatty acid synthesis 
      (FAS II) pathway, to initiate the formation of pimeloyl-ACP, a precursor of 
      biotin synthesis. To further explore molecular basis of BioZ activity, we 
      determine the crystal structure of Agrobacterium tumefaciens BioZ at 1.99 A, of 
      which the catalytic triad and the substrate-loading tunnel are functionally 
      defined. In particular, we localize that three residues (S84, R147, and S287) at 
      the distant bottom of the tunnel might neutralize the charge of free C-carboxyl 
      group of the primer glutaryl-CoA. Taken together, this study provides molecular 
      insights into the BioZ biotin synthesis pathway.
FAU - Zhang, Sitao
AU  - Zhang S
AD  - Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key 
      Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical 
      Research Center of South China, Key Laboratory of OptoElectronic Science and 
      Technology for Medicine of the Ministry of Education, College of Life Sciences, 
      Fujian Normal University, Fuzhou, Fujian, China.
AD  - Department of Pathogen Biology & Microbiology and General Intensive Care Unit of 
      Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 
      Zhejiang, China.
FAU - Xu, Yongchang
AU  - Xu Y
AD  - Department of Pathogen Biology & Microbiology and General Intensive Care Unit of 
      Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 
      Zhejiang, China.
FAU - Guan, Hongxin
AU  - Guan H
AD  - Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key 
      Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical 
      Research Center of South China, Key Laboratory of OptoElectronic Science and 
      Technology for Medicine of the Ministry of Education, College of Life Sciences, 
      Fujian Normal University, Fuzhou, Fujian, China.
FAU - Cui, Tao
AU  - Cui T
AD  - School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, 
      China.
FAU - Liao, Yuling
AU  - Liao Y
AD  - Guangdong Provincial Key Laboratory of Protein Function and Regulation in 
      Agricultural Organisms, College of Life Sciences, South China Agricultural 
      University, Guangzhou, Guangdong, China.
FAU - Wei, Wenhui
AU  - Wei W
AD  - Department of Pathogen Biology & Microbiology and General Intensive Care Unit of 
      Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 
      Zhejiang, China.
FAU - Li, Jun
AU  - Li J
AD  - Department of Pathogen Biology & Microbiology and General Intensive Care Unit of 
      Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 
      Zhejiang, China.
AD  - Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of 
      Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 
      Zhejiang, China.
FAU - Hassan, Bachar H
AU  - Hassan BH
AD  - Stony Brook University, Stony Brook, NY, USA.
FAU - Zhang, Huimin
AU  - Zhang H
AD  - Department of Pathogen Biology & Microbiology and General Intensive Care Unit of 
      Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 
      Zhejiang, China.
AD  - Carl R. Woese Institute for Genomic Biology, University of Illinois at 
      Urbana-Champaign, Urbana, IL, USA.
FAU - Jia, Xu
AU  - Jia X
AD  - Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu 
      Medical College, Chengdu, Sichuan, China.
FAU - Ouyang, Songying
AU  - Ouyang S
AUID- ORCID: 0000-0002-1120-1524
AD  - Laboratory of Innate Immune Biology of Fujian Province, Provincial University Key 
      Laboratory of Cellular Stress Response and Metabolic Regulation, Biomedical 
      Research Center of South China, Key Laboratory of OptoElectronic Science and 
      Technology for Medicine of the Ministry of Education, College of Life Sciences, 
      Fujian Normal University, Fuzhou, Fujian, China. ouyangsy@fjnu.edu.cn.
FAU - Feng, Youjun
AU  - Feng Y
AUID- ORCID: 0000-0001-8083-0175
AD  - Department of Pathogen Biology & Microbiology and General Intensive Care Unit of 
      Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 
      Zhejiang, China. fengyj@zju.edu.cn.
AD  - Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu 
      Medical College, Chengdu, Sichuan, China. fengyj@zju.edu.cn.
AD  - College of Animal Science, Zhejiang University, Hangzhou, Zhejiang, China. 
      fengyj@zju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210406
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (Acyl Carrier Protein)
RN  - 0 (Acyl Coenzyme A)
RN  - 0 (Escherichia coli Proteins)
RN  - 3131-84-8 (glutaryl-coenzyme A)
RN  - 6SO6U10H04 (Biotin)
SB  - IM
MH  - Acyl Carrier Protein/metabolism
MH  - Acyl Coenzyme A/metabolism
MH  - Agrobacterium/growth & development
MH  - Amino Acid Sequence
MH  - Biocatalysis
MH  - *Biosynthetic Pathways
MH  - Biotin/*biosynthesis
MH  - Crystallography, X-Ray
MH  - Escherichia coli/*metabolism
MH  - Escherichia coli Proteins/*chemistry/*metabolism
MH  - Molecular Docking Simulation
MH  - Phylogeny
MH  - Protein Multimerization
MH  - Structural Homology, Protein
MH  - Substrate Specificity
PMC - PMC8024396
COIS- The authors declare no competing interests.
EDAT- 2021/04/08 06:00
MHDA- 2021/04/15 06:00
PMCR- 2021/04/06
CRDT- 2021/04/07 06:05
PHST- 2019/11/22 00:00 [received]
PHST- 2021/03/12 00:00 [accepted]
PHST- 2021/04/07 06:05 [entrez]
PHST- 2021/04/08 06:00 [pubmed]
PHST- 2021/04/15 06:00 [medline]
PHST- 2021/04/06 00:00 [pmc-release]
AID - 10.1038/s41467-021-22360-4 [pii]
AID - 22360 [pii]
AID - 10.1038/s41467-021-22360-4 [doi]
PST - epublish
SO  - Nat Commun. 2021 Apr 6;12(1):2056. doi: 10.1038/s41467-021-22360-4.