Synthetic Biology in China  – About the Industrialization of Biology

Synthetic Biology in China – About the Industrialization of Biology

Loading
Loading Social Plug-ins...
Language: English
Save to myLibrary Download PDF
Go to Page # Page of 29

Description: Synthetic Biology in China – About the Industrialization of Biology. Synthetic Biology in China– About the “Industrialization of Biology” Scientific Implication Technology Innovation Engineering Integration Industrial Application. Synthetic Biology projects funded by the 973 program National Basic Research Program of China 973 China Artificial cell factory (chemicals) Photosynthesis and artificial leaf Artificial systems for high - yield production of microbial drugs New functional bio devices (drug and food) New pathways for biological materials Standardization of biological components, modules, construction of module library Industrial, agricultural or medicine applications.

Pollution of Air, Water and Garbage in China is probably one of the worst in the world. (Environmental issues) Severe problems in esertification, water and soil erosion , and loss of biodiversity. (Ecological issues), The Key Challenge Imbalance b/w Population + development vs Nature resource supply + regeneration.

Historical Aspect: Starting from fermentation – Classical microbiology and biotechnology, Fermentation and classical genetics, Physiology, Biochemistry, Molecular genetics. ABE semi – continuous fermentation started in the 1950’s Comparison of DNA integration efficiency b/w non -replicative plasmid. Genomics : Genome sequencing and functional genomics Comparative and evolution genomics, Life “Omics ” and systems biology: Transcriptome and expression regulation Metabolome and metagenome Prot ...Please navigate Paper pages for more details.

 
Author: Guo-Ping ZHAO (Fellow) | Visits: 1146 | Page Views: 1375
Domain:  Medicine Category: Biotech/Pharma Subcategory: Business 
Upload Date:
Link Back:
Short URL: http://www.wesrch.com/medical/pdfME1XXFCJ4JSRS
Loading
Loading...



px *        px *

* Default width and height in pixels. Change it to your required dimensions.

 
Contents:
Synthetic Biology in China

– About the “Industrialization of Biology”
Scientific Implication
Technology Innovation
Engineering Integration
Industrial Application

Guo-Ping ZHAO

(email: gpzhao@sibs.ac.cn)
Key Laboratory of Synthetic Biology (KLSynB)
Institute of Plant Physiology and Ecology (IPPE)
Shanghai Institutes for Biological Sciences (SIBS)
Chinese Academy of Sciences (CAS)

The National Academies, Washington, DC, USA
May 28, 2014

Outlines
1. Synthetic biology in China: Foundation and
Initiation – Overview
2. Historical Aspect: Starting from fermentation –
Classical microbiology and biotechnology
3. Fundamental Aspect: Bridging by genomics – Life
“omics” and systems biology
4. Innovation Aspect: New era of synthetic biology –
Synthetic engineering of biological systems
5. Organizational Aspect: Institutional reform and
organization – KLSynB

Foundations

Bioengineeting/Biotechnology/
Metabolic engineering

Computational
biology

Genomics
“Omics”

Chinese
Foundations of
SynBio
Structure Biology

Total synthesis
of Bovine
Insulin and
Yeast tRNAAla

Initiation

Chemistry
Biochemistry

Bioinformatics

2005: First review. Participation of iGEM
2008: Xiangshan Symposium (NSFC CAS)
Key laboratory (KLSynB, CAS)
2009: Oriental Symposium (Shanghai CAE)
2010: State key program for basic research
(Cell factory, chassis, minimal genome)
2011: State key program for basic research
(Parts, modules, pathways, networks)

Synthetic Biology projects
funded by the 973 program
Artificial cell factory (chemicals)
Photosynthesis and artificial leaf
Artificial systems for high-yield production
of microbial drugs

New functional biodevices (drug and food)

973
China

National Basic
Research
Program of China

New pathways for biological materials
Standardization of biological components,
modules, construction of module library
Industrial, agricultural or medicine
applications

Drinking

Challenge of the century: Sustainable
Development
Travel

China imports:
• 1/3 of “agriculture
Health and medical care
products”
Housing • 1/2 of natural gas and oil
Food
for all the people
• Economical issues
Clothing

• Pollution of Air, Water and Garbage
in China is probably one of the worst
in the world. (Environmental issues)
• Severe problems in desertification,
water and soil erosion, and loss of
biodiversity. (Ecological issues)
• The Key Challenge:Imbalance b/w
Population + development vs Nature
resource supply + regeneration

World
Population

Historical Aspect: Starting from
fermentation – Classical microbiology
and biotechnology






Fermentation and classical genetics
Physiology
Biochemistry
Molecular genetics

EA2018 CCTCC M94061 the 721 strain, industrialized
Soil

(66% butanol)
(9.69 g/L solvent)
↓EMS
mutation
selection/screening

EB20
(67.2% butanol)
(13.09 g/L solvent)
↓ EMS
mutation
selection/screening

EA2018
(69.7% butanol)
(19.163 g/L solvent)

Corn

A
Seed

E
ABE semicontinuous
fermentation
started in the
1950’s
ATCC 824:60% n-butanol
Clostridium acetobutylicum
EA2018 CCTCC M94061

Ni and Sun, BBSRC China partner Workshop, 2009

water

B

Gene knock-out in Clostridium acetobutylicum
pSY6-buk

pSY6-solR

+37%

+44%

http://www.sigmaaldrich.com/sigma/general%2
0information/targetron_poster.pdf

Comparison of DNA integration
efficiency b/w non-replicative plasmid
versus

Targetron
buk: butyrate kinase

pJC4BK & pDHSR: non-replicative integration plasmid
pSY6-buk & pSY6-solR: TargeTron plasmid

solR: “sol operon repression gene”?
Shao, L. et al 2007. Cell Res

Fundamental Aspect:
Bridging by genomics
– Life “omics” and systems biology


Genomics:
Genome sequencing and functional genomics
Comparative and evolution genomics



Life “Omics” and systems biology:
Transcriptome and expression regulation
Metabolome and metagenome
Proteome and acetolome

Microbial
Genomes
101Mb
1% HGP BACbased
sequencing

400Mb
102Mb

Primary
Sequence

3rd
PacBio

100kb
100Mb
1st ABI 37003730
MegaBase1000 2nd First Roche/454
4000
Solexa=Illumina
Ion Torrent
Comparative genomics
Evolution genomics

Single cell genomics
Pan-genomics
Meta-genomics

Comparative genomic and
transcriptomic analyses
revealed genetic
characteristics related to
solvent formation and xylose
utilization in Clostridium
acetobutylicum EA 2018
Shiyuan et al. (2011)

adc knock-out

802
Strain

No acetone production, 80% butanol (2008)
pSY6-adc

Emr

adc:acetoacetate decarboxylase

adc
Strain

medium

Butanol
%

2018p

P2

71±1

2018p

P2/CaCO3

72±0.6

2018p

P2/CaCO3/methyl viologen

71.6±0.1

2018adc P2

80±0

2018adc P2/CaCO3

74.3±0.4

2018adc P2/CaCO3/methyl viologen

82±2

Jiang Y. et al 2009. Metab Eng

Innovation Aspect: New era of synthetic biology –
Synthetic engineering for biological systems
• Systems biology and synthetic biology
• Innovation in enabling technology
• Towards engineering:
Parts, modules, circuits, chassis cells
• Towards application:
Serving social/economical developments

Synthetic biology: Discovery → Innovation
Core of Molecular Biology
Translation

Transcription

mRNA

DNA
Core of
“Omics”

Initiation
Discovery
phase

Genome

Transcriptome

Catalysis

Protein

Metabolites

Proteome

Metabalome

2000

1990
Top-down strategy

Reverse engineering

Systems Biology

Innovation
phase

Parts
Devices
Modules

Synthetic Biology
Bottom-up strategy
Forward engineering

Pathway
Network
Regulation

Enabling Technology
• Quantitative biology technology:
Measuring and quantitation
• Bioinformatics technology:
Analysis and design
• Bioengineering technology:
Standardized registry
• DNA synthesis+recombination technology:
High efficiency and accuracy
• Systems biology technology:
Tuning and optimization

Reconstruction of butanol pathway: 95% butanol (2010)

901
Strain

EA2018

Jiang Y. unpublished

Feedstock dominates the variable
cost for solvent production
12 biobutanol plants restored since 2006

Butanol price (RMB/t)

oil price $/barrel

• Not to use grains for the
production of commodity
• Not to use gasoline for
the production of food
Distribution of variable cost for solvent production (data from NCPC)

Xylose metabolism of Clostridium acetobutylicum

木糖利用
Gu Y. et al 2010. BMC Genomics

Identification of xylose-catabolic genes and reconstruction of
xylose-metabolic pathway in C. acetobutylicum
xylA

xylB

tal

tkl

ptb promotor
Bam HI

tal
Sma I

mslR

pIMP1-TAL

5758 bp

Significant improvement in
xylose utilization

bla
ori

25
20

g/L

15
10

Bioinformatic analysis and identification
of genes involved in xylose metabolism
Y. Gu, et al. BMC Genomics, 2010

5
0
wild type

wild type

mutant

mutant

n-Butanol from Corn Stover Hydrolysate/corncob by
engineered Clostridium
corncob

4-5% sugar
Pretreatment

cellulase

Continuous
Sterilization

Steam

Fermentation

Water
strain
0.4

0.34

0.35

Solvent yield

Corn stover

0.3

Distillation

acid

hydrolysis

0.275

0.25
0.2
0.15
0.1
0.05
0
8052

8052xylRxylT
CIBTS0795*

82% of the theoretical yield
WO2012159571

C5(pentose) yeast for lignocellulosic ethanol
ETHANOL

Hexose
Pentose

Inhibitors

2G Ethanol Pilot of COFCO in Zhaodong

Metabolic engineering enables Saccharomyces
cerevisiae to utilize xylose
Xylose
GXF1
Xylose (in)
XI

Glycolysis

Xylulose

Inhibitors

XKS1

Formate
FDH

D-Xylulose-5-P

CO2 + NADH

Pentose phosphate pathway
non-oxidative enzymes
(RPE1, RKI1, TAL1, TKL1)

Glyceraldehyde-3-P

Organic acids
Salts
HMF & Furfural
Phenols

Xylitol

Na+

Na+

Ethanol (in)

SO42-

Ethanol

Diao BMC Biotechnol in revision

Evolutionary engineering significantly enhance
xylose consumption rate in rich medium

Xylose conc. g/l

……

45
40
35
30
25
20
15
10
5
0

Consumed
Residual

Residual
Consumed

1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
190 352 430 573 712 905 1074 1175 1340 1508 1681 1840 1944 2057 2116 2183 2223 2248 2272

Evolution time, h

Diao BMC Biotechnol 2014

Residual
Residual
Residual
Residual
Residual
Residual
Residual
Residual
Residual
Residual
Residual
Residual
Residual

Residual

0
1
1
1
2
1
1
2
1
2
1
2
1
2
1
2
1
2
1
2
4 1 1 5 22 6
1
1
2
1
2
1
1
2
1
2
1
2
1
1
2
1
1
2
0 0 1 1 2 2
1

0

3

1

8

2

2
3
4
5
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
3
3 7 4 8 5 59 6 10 7
4
6
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
3
4
5
6
3 4 4 5 5 6 6
3

3

35 55

4

59

5

6

Consumed
Consumed
Consumed
Consumed
Consumed
Consumed
Consumed
Consumed
Consumed
Consumed
Consumed
Consumed
Consumed

Consumed

67
78
89
910 10
10
11 11
12 1213 1314 1415 1516 1617 1718 1819 19
13
14
15
11
12
16
17
18
19
8
9
10
11
12
13
14
15
16
17
18
19
7
10
11
12
13
14
15
16
17
18
19
8
9
10
11
12
13
14
15
16
17
18
19
7
10
11
12
13
14
15
16
17
18
19
8
9
10
11
12
13
14
15
16
17
18
19
7
10
11
12
13
14
15
16
17
18
19
8
9
10
11
12
13
14
15
16
17
18
19
7
10
11
12
13
14
15
16
17
18
19
11 8 128 9 13 9 10 14 10 15 11 16 12 17 14 18 15 19 1615 17 16 18 17 19 18
11
12
13
13
14
19
7
10
11
12
13
14
15 Na+
16
17
18
19
8
9
10
11
12
13
14
15
16
17
18
19
7
10
11
12
13
14
15
16
17
18
19
8
9
10
11
12
13
14
15
16
17
18
19
7
10
11
12
13
14
15
16
17
18
19
9
10
11
12
13
14
15
16
17
18
19
7
8
10
11
12
13
14
15
16
17
18
19
9
10
11
12
13
14
15
16
17
18
19
7
8
10
11
12
13
14
15
16
17
18
19
8
9
10
11
12
13
14
15
16
17
18
19
7
10
11
12
13
14
15
16
17
18
19
7 8 8 9 9 10 10 11 11 12 12 13 13 14 14 15 15 16 16 17 17 18 18 19 19
7
10
11
12
13
14
15
16
17
18
19
SO42-

7

8

9

10

11

12

13

14

15

16

17

18

19

69 73 75 91 97 103 109 113 119 141 147 168 172 178

No. of transfer (generations)

45
40
35
30
25
20
15
10
5
0
100
87.5
75
62.5
50
37.5
25
12.5
0

Inhibitor conc. %

Xylose Xylose conc.
conc. conc.
XyloseXyloseg/lg/lg/lg/lg/lg/l
conc.
Xylose Xylose conc.
Xylose Xylose conc.
conc.
conc. conc.
XyloseXyloseg/lg/lg/lg/lg/lg/l
Xylose Xylose conc.
conc. conc.
Xylose conc. g/l

4545
4545
4545
4040
4545
4040
4545
4040
3535
45
4545
4040
3540
4535
45
4030
3535
3040
4545
40
4035
3530
3035
4545
4040
3525
3030
4540
45
2535
4045
35
3530
3025
4545
2530
4035
40
3520
4545
3035
2525
4040
2030
3540
30
3025
2520
4040
2025
3530
3015
4035
2530
2020
3540
35
1525
3035
25
2520
2015
3535
1520
3025
30
2510
3535
2025
1515
3030
1020
2530
20
2015
1510
3020
1015
2525
2030
3030
1520
1010
2525
5 5
2025
15
1515
1010
2525
5 5
2015
1510
2520
1015
510
5
2025
20
0 5
15 0
10
1020
5 0
2020
0 5
1515
1010
2020
5 00
0 15
1510
1015 5
5 50
0 0
1515
0
1010
5 5
1515
0 00
1010 0
510
5
0 300
1010
5 5
2 1010
0 0
0
50
5
0 5
5 50
0 0
0
5 5
0 0
0 00
00
0 0
0

Xylose conc. g/l

Evolutionary engineering significantly enhance xylose
consumption rate in the presence of inhibitors

Plants of biobutanol and 2G ethanol in China
Jilin Zhonghai

Jilin Fuel Ethanol

Laihe-Rockley

COFCO (Zhaodong)

5,000 t/y

3,000 t/y, planned

100,000 t/y

500 t/y
Heilongjiang Haohua
5,000 t/y

Hebei Jizhou

Zhongketianyuan
10000 t/y

3,000 t/y

Cathay (Jilin)
30,000 t/y
Shandong Zesheng
3,000 t/y
Tangshan Jidong
5,000 t/y
Lianyungang Lianhua
40,000 t/y
Shandong Longlive

50,000 t/y

Henan Tianguan
30,000 t/y
10,000 t/y

Jinan Shengquan
20,000 t/y

COFCO (Anhui)

Guangxi Jinyuan

Jiangsu Jinmaoyuan

Jiangsu Lianhai

5,000 t/y

50,000 t/y

30,000 t/y

50,000 t/y

25-31

Engineered strains ready for pilot scale
lignocellulosic biofuel production
Xylose

Xylose

XylT

GXF1

Xylose
D-Glucose-P

Xylose (in)

XylR

XI

XylA
L-Arabinose

Xylulose

AraR

Hexose Pentose
Xylulose-5-P
FBP

Hpr

PPP
ATP
HprK/P

ADP
Hpr-P-Ser

Acetone

cre

Glycolysis

XylB

Hpr-P-His

gene

CcpA

Inhibitors

Clostridia

Furfural
Organic acids
Salts
HMF
Phenolics SO42-

Ethanol
n-Butanol

XKS1

Formate
FDH

D-Xylulose-5-P

CO2 + NADH

Pentose phosphate pathway
non-oxidative enzymes
(RPE1, RKI1, TAL1, TKL1)

Glyceraldehyde-3-P
Na+

Xylitol

Ethanol (in)

Na+

Organizational Aspect:
From the West Bund to the East Bund of Shanghai:
Life science research and biotechnology development
The West Bund

SIBS
IBC/CB

Proteomics
Center

Fudan
Univ.

ION
Experimental Animal Inst. Nutrition
Institute of
Facilities
Shanghai
Computational Biol.
Pasteur
IPPE Bioinformatics
Shang
Center
Inst. Health 
Zhang-Jiang
JiaoTong Science
NGRC
HiTech Park
Univ.
IMM
( E. Bund )
(East Bund)

BioTech Centers

The East Bund:
Vision of Zhang Jiang Biopharmaceutical Valley
CHGCS

BioChip Center

Mechanism of Disease/Drugs

Drug Screening Center

Synchrotron
Synchrotron

Biological Targets
Biological Targets

X-Ray, NMR, E/M, etc

Purification

Structure of
Bio-macromolecules

Nature Products
CombiChem

Lead
Biological
Screening Compounds

Inst. Material Medica
TCM Research Center

Shanghai Univ Chinese Medicine

Biological
Screening

Optimization
(Structure/Function)

Structure Based
Drug Design

Bioinformatics
Center of Model Animals

Drug Candidates
Drug Safety Evaluation

Clinical Research

Hospital/GLP)

Clinical Trials
SFDA Approval

New Drug

Center

CAS-Key Laboratory of Synthetic Biology (KLSynB)
Theoretical/Technological
Research

Cloud

State Key
Lab for
Plant Mol Genetics

IPPE-Lab for
Photosynthesis
Environmental
Biology

Multidisciplinary research

KL Core KL
SynB
SysB

CAS-Key
Industry
Lab for
Insect Science Biotechnology

Center

Applied
Research

SIBS
Inst. Organic Chem
CUST, Fudan, SJTU
Res Institutions+Tech Platforms

Bioinformatics
technology
center

Tech R&D

Route

CHGC-SBC
“Omics” centers

“Omics”
Research
Platforms

Biomedicine
Translational
Research
Center
Translational

Research

Energy, Environment, Chemical industry,
Pharmaceutics, Medicine, Health……

Subscribe
x