PMID- 26519464
OWN - NLM
STAT- MEDLINE
DCOM- 20160426
LR  - 20190109
IS  - 1362-4962 (Electronic)
IS  - 0305-1048 (Print)
IS  - 0305-1048 (Linking)
VI  - 43
IP  - 21
DP  - 2015 Dec 2
TI  - Algorithmic co-optimization of genetic constructs and growth conditions: 
      application to 6-ACA, a potential nylon-6 precursor.
PG  - 10560-70
LID - 10.1093/nar/gkv1071 [doi]
AB  - Optimizing bio-production involves strain and process improvements performed as 
      discrete steps. However, environment impacts genotype and a strain that is 
      optimal under one set of conditions may not be under different conditions. We 
      present a methodology to simultaneously vary genetic and process factors, so that 
      both can be guided by design of experiments (DOE). Advances in DNA assembly and 
      gene insulation facilitate this approach by accelerating multi-gene pathway 
      construction and the statistical interpretation of screening data. This is 
      applied to a 6-aminocaproic acid (6-ACA) pathway in Escherichia coli consisting 
      of six heterologous enzymes. A 32-member fraction factorial library is designed 
      that simultaneously perturbs expression and media composition. This is compared 
      to a 64-member full factorial library just varying expression (0.64 Mb of DNA 
      assembly). Statistical analysis of the screening data from these libraries leads 
      to different predictions as to whether the expression of enzymes needs to 
      increase or decrease. Therefore, if genotype and media were varied separately 
      this would lead to a suboptimal combination. This is applied to the design of a 
      strain and media composition that increases 6-ACA from 9 to 48 mg/l in a single 
      optimization step. This work introduces a generalizable platform to co-optimize 
      genetic and non-genetic factors.
CI  - (c) The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic 
      Acids Research.
FAU - Zhou, Hui
AU  - Zhou H
AD  - Synthetic Biology Center, Department of Biological Engineering, Massachusetts 
      Institute of Technology, Cambridge, MA 02139, USA.
FAU - Vonk, Brenda
AU  - Vonk B
AD  - DSM Biotechnology Center, PO Box 1, 2600 MA Delft, The Netherlands.
FAU - Roubos, Johannes A
AU  - Roubos JA
AD  - DSM Biotechnology Center, PO Box 1, 2600 MA Delft, The Netherlands.
FAU - Bovenberg, Roel A L
AU  - Bovenberg RA
AD  - DSM Biotechnology Center, PO Box 1, 2600 MA Delft, The Netherlands Synthetic 
      Biology and Cell Engineering, Groningen Biomolecular Sciences and Biotechnology 
      Institute, University of Groningen, Groningen, The Netherlands.
FAU - Voigt, Christopher A
AU  - Voigt CA
AD  - Synthetic Biology Center, Department of Biological Engineering, Massachusetts 
      Institute of Technology, Cambridge, MA 02139, USA cavoigt@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151030
PL  - England
TA  - Nucleic Acids Res
JT  - Nucleic acids research
JID - 0411011
RN  - 0 (Culture Media)
RN  - U6F3787206 (Aminocaproic Acid)
SB  - IM
MH  - *Algorithms
MH  - Aminocaproic Acid/*metabolism
MH  - Culture Media
MH  - Escherichia coli/genetics/growth & development
MH  - Metabolic Engineering/*methods
MH  - Metabolic Networks and Pathways/genetics
PMC - PMC4666358
EDAT- 2015/11/01 06:00
MHDA- 2016/04/27 06:00
PMCR- 2015/10/30
CRDT- 2015/11/01 06:00
PHST- 2015/10/01 00:00 [accepted]
PHST- 2015/07/22 00:00 [received]
PHST- 2015/11/01 06:00 [entrez]
PHST- 2015/11/01 06:00 [pubmed]
PHST- 2016/04/27 06:00 [medline]
PHST- 2015/10/30 00:00 [pmc-release]
AID - gkv1071 [pii]
AID - 10.1093/nar/gkv1071 [doi]
PST - ppublish
SO  - Nucleic Acids Res. 2015 Dec 2;43(21):10560-70. doi: 10.1093/nar/gkv1071. Epub 
      2015 Oct 30.