PMID- 32474798
OWN - NLM
STAT- MEDLINE
DCOM- 20210224
LR  - 20210224
IS  - 1432-0614 (Electronic)
IS  - 0175-7598 (Linking)
VI  - 104
IP  - 14
DP  - 2020 Jul
TI  - Identification and importance of mitochondrial citrate carriers and ATP citrate 
      lyase for glycolipid production in Starmerella bombicola.
PG  - 6235-6248
LID - 10.1007/s00253-020-10702-z [doi]
AB  - Starmerella bombicola is a non-conventional yeast commercially used as a 
      microbial cell factory for sophorolipid production. Sophorolipids are glycolipid 
      biosurfactants composed of a glucose disaccharide sophorose and a fatty acid. In 
      de novo sophorolipid synthesis, the fatty acid moiety is derived from the fatty 
      acid synthesis (FAS) complex; therefore, the yeast's lipid metabolism plays a 
      crucial role in sophorolipid biosynthesis. As a fatty acid precursor, citric acid 
      is a key primary metabolite that connects carbohydrate and lipid metabolism, and 
      in S. bombicola, it also has a regulatory effect on sophorolipid composition and 
      productivity. We aimed to identify the mitochondrial transporters involved in 
      citrate shuttling and the ATP citrate lyase (Acl), the enzyme that converts 
      citric acid into acetyl-CoA. Subsequently, we studied their role in the citric 
      acid shuttle and glycolipid synthesis and the potential of citrate metabolism as 
      a genetic manipulation target for increased glycolipid synthesis. Bioinformatics 
      analyses predicted 32 mitochondrial carriers of which two were identified as 
      citrate transporters, named SbCtp1 and SbYhm2. Deletion of these mitochondrial 
      carriers led to a lesser sophorolipid yield and a shift in the lactonic/acidic 
      sophorolipid ratio. However, only the knockout of SbYhm2 caused a decrease of 
      citric and an increase of malic acid extracellular concentrations. Additionally, 
      deletion of SbAcl1 had a negative effect on S. bombicola's specific growth rate 
      and sophorolipid synthesis and contributed to extra- and intracellular citric 
      acid accumulation. Unexpectedly, SbAcl1 overexpression also decreased glycolipid 
      production.Key Points* Starmerella bombicola is an industrially relevant 
      microbial cell factory for biosurfactant production.* There are 32 predicted 
      mitochondrial carriers in S. bombicola.* Citrate mitochondrial carriers SbYhm2 
      and SbCtp1 are essential for glycolipid synthesis in S. bombicola.* Deletion of 
      SbAcl1 negatively affects growth and sophorolipid production in S. bombicola. 
      Graphical abstract.
FAU - Jezierska, Sylwia
AU  - Jezierska S
AUID- ORCID: 0000-0001-8810-3167
AD  - Centre for Synthetic Biology, Department of Biotechnology, Ghent University, 
      Coupure Links 653, 9000, Ghent, Belgium.
FAU - Claus, Silke
AU  - Claus S
AD  - Centre for Synthetic Biology, Department of Biotechnology, Ghent University, 
      Coupure Links 653, 9000, Ghent, Belgium.
FAU - Van Bogaert, Inge N A
AU  - Van Bogaert INA
AD  - Centre for Synthetic Biology, Department of Biotechnology, Ghent University, 
      Coupure Links 653, 9000, Ghent, Belgium. Inge.VanBogaert@Ugent.be.
LA  - eng
GR  - 151610/Fonds Wetenschappelijk Onderzoek/
GR  - 1117519N/Fonds Wetenschappelijk Onderzoek/
GR  - IWT80050/Agentschap voor Innovatie door Wetenschap en Technologie/
PT  - Journal Article
DEP - 20200530
PL  - Germany
TA  - Appl Microbiol Biotechnol
JT  - Applied microbiology and biotechnology
JID - 8406612
RN  - 0 (Carrier Proteins)
RN  - 0 (Citrates)
RN  - 0 (Fungal Proteins)
RN  - 0 (Glycolipids)
RN  - 0 (Malates)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Oleic Acids)
RN  - 0 (sophorolipid)
RN  - 817L1N4CKP (malic acid)
RN  - EC 2.3.3.8 (ATP Citrate (pro-S)-Lyase)
RN  - Starmerella bombicola
SB  - IM
MH  - ATP Citrate (pro-S)-Lyase/genetics/*metabolism
MH  - Amino Acid Sequence
MH  - Biological Transport
MH  - Carrier Proteins/genetics/*metabolism
MH  - Citrates/*metabolism
MH  - Fungal Proteins/genetics/metabolism
MH  - Glycolipids/*biosynthesis
MH  - Malates/metabolism
MH  - Mitochondrial Proteins/genetics/*metabolism
MH  - Molecular Structure
MH  - Mutation
MH  - Oleic Acids/biosynthesis/chemistry
MH  - Phylogeny
MH  - Saccharomycetales/classification/genetics/growth & development/*metabolism
OTO - NOTNLM
OT  - ATP citrate lyase
OT  - Glycolipid
OT  - Mitochondrial carriers
OT  - Sophorolipid
OT  - Starmerella bombicola
OT  - Yeast
EDAT- 2020/06/01 06:00
MHDA- 2021/02/25 06:00
CRDT- 2020/06/01 06:00
PHST- 2020/03/16 00:00 [received]
PHST- 2020/05/24 00:00 [accepted]
PHST- 2020/05/19 00:00 [revised]
PHST- 2020/06/01 06:00 [pubmed]
PHST- 2021/02/25 06:00 [medline]
PHST- 2020/06/01 06:00 [entrez]
AID - 10.1007/s00253-020-10702-z [pii]
AID - 10.1007/s00253-020-10702-z [doi]
PST - ppublish
SO  - Appl Microbiol Biotechnol. 2020 Jul;104(14):6235-6248. doi: 
      10.1007/s00253-020-10702-z. Epub 2020 May 30.