David James

Department of Chemical and Biological Engineering

ChELSI Institute

Bioenergy and

Industrial Biotechnology

“Industrial Biotechnology (IB) is a set of cross-disciplinary technologies that

use biological resources for producing and processing materials and chemicals

for non-food applications. These resources can be derived from the tissues,

enzymes and genes of plants, algae, marine life, fungi and micro-organisms.”

“Bioenergy is a renewable form of energy generated from materials derived from

biological sources. Bioenergy is increasingly being recognised as having an

important role in helping the UK to maintain its energy security in the context of

diminishing worldwide stocks of fossil fuels.”

http://www.bbsrc.ac.uk/funding/priorities/ibb-bioenergy.aspx

http://www.bbsrc.ac.uk/funding/priorities/ibb-industrial-biotechnology.aspx

0

20

40

60

80

100

120

140 N

o. of

BB

SR

C g

rants

*

WRC Oxbridge WRC Oxbridge WRC Oxbridge

Industrial

Biotechnology

UK total = 793

Bioenergy

UK total = 108

Synthetic

Biology

UK total = 1245

*Total current grants including studentships and project funding

BBSRC Funded Research: How Are We Doing?

Cross-Cutting Enabling Technologies

Facilitate Bioenergy and IB Research

Chemical

Engineering

Materials

Engineering

Systems

Biology

Synthetic

Biology

Computational

Biology

Metabolic

Engineering

Structural

Biology

Cell/Molecular

Biology

Bioinformatics

„Omics

Measure

Model

Manipulate

Manufacture

Design

Principles

The Engineering

Design Approach

Yields Predictable

Solutions

http://www.bbsrc.ac.uk/funding/priorities/enww-

synthetic-biology.aspx

http://www.bbsrc.ac.uk/news/research-technologies/2012/121102-n-ikc-

synthetic-biology.aspx

http://www.bbsrc.ac.uk/publications/topic/biology-by-design.aspx

An abstraction hierarchy that supports the engineering of

integrated genetic systems. Endy. D. Nature (2005)

Simulating the Cell: Modelling

and Computational Biology

BBSRC

Budget

2011-2012

£445M!

Predicted bioenergy percent of UK

Energy in 2050 is 12%

http://www.bbsrc.ac.uk/funding/priorities/ibb-bioenergy.aspx

http://www.bbsrc.ac.uk/publications/plannin

g/strategy/priority-bioenergy.aspx

Fuel

Second Generation,

Sustainable, Bacterial Biofuels Nigel Minton (Nottingham)

• Newcastle University

• TMO Renewables Ltd

ENVIRONMENTAL, SOCIAL, ECONOMIC SUSTAINABILITY

Perennial

Bioenergy

Crops

(BSBEC-

BioMASS) Angela Karp

(Rothamsted) • IBERS

• Imperial College

• University of

Cambridge

• Ceres Inc

Cell Wall Sugars Paul Dupree

(Cambridge)

• Newcastle University

• Novozymes A/G

Cell Wall Lignin Claire Halpin

(Dundee)

•University of York

•SCRI

•RERAD

•Limagrain UK Ltd

•Syngenta

•AgroParisTec – INRA

Marine

Wood Borer

Enzyme Discovery Simon McQueen-

Mason

(York)

• University of Portsmouth

• Novozymes

Lignocellulosic Conversion to

Bioethanol Katherine Smart (Nottingham)

• University of Bath • University of Surrey

• BP • Bioethanol Ltd

• Briggs of Burton • British Sugar Ltd

• Coors Brewers Ltd • DSM

• Ethanol Technology Ltd • HGCA

• Pursuit Dynamics • SABMiller

• Scottish Whisky Research Institute

Tackling major barriers of sustainable biofuel production

Six integrated programmes; 20 million investment

Marine Wood Borer Enzyme Discovery

Simon McQueen-Mason and Neil Bruce Simon Cragg

Limnoria quadripunctata

is a marine isopod that

lives on a diet of wood,

and has a digestive tract

devoid of microbial life.

The Limnoriid gut is

effectively an enzyme

reactor for lignocellulose

mobilisation

Singletons

(not annotated)

18.3%

Proteases

2.7%

GH Family

proteins

27.0%

Other sequences

29.7%

Leucine-rich

repeat proteins

2.7%

Hemocyanins

17.3%

Ferritins

1.1%

Fatty acid binding

protein

1.3% GH7

53.3%

GH9

37.0%

GH30

1.5%

GH5

3.9%

Others

1.6%GH35

2.7%

A

B C

D ESingletons

(not annotated)

18.3%

Proteases

2.7%

GH Family

proteins

27.0%

Other sequences

29.7%

Leucine-rich

repeat proteins

2.7%

Hemocyanins

17.3%

Ferritins

1.1%

Fatty acid binding

protein

1.3% GH7

53.3%

GH9

37.0%

GH30

1.5%

GH5

3.9%

Others

1.6%GH35

2.7%Singletons

(not annotated)

18.3%

Singletons

(not annotated)

18.3%

Proteases

2.7%

Proteases

2.7%

GH Family

proteins

27.0%

GH Family

proteins

27.0%

Other sequences

29.7%

Other sequences

29.7%

Leucine-rich

repeat proteins

2.7%

Leucine-rich

repeat proteins

2.7%

Hemocyanins

17.3%

Hemocyanins

17.3%

Ferritins

1.1%

Ferritins

1.1%

Fatty acid binding

protein

1.3%

Fatty acid binding

protein

1.3% GH7

53.3%

GH7

53.3%

GH9

37.0%

GH9

37.0%

GH30

1.5%

GH30

1.5%

GH5

3.9%

GH5

3.9%

Others

1.6%

Others

1.6%GH35

2.7%

GH35

2.7%

A

B C

D E

• Identifying the mechanisms of wood digestion in

Limnoriids

• Using transcriptomic and proteomic studies to

identify key enzymes in this process

• Producing and characterising recombinant

versions of these enzymes

• Working with industry to examine utility of these

enzymes

Research Focus

LqGH7B is our best characterised enzyme

95

72

55

36 28

CF FT CC D B2 B3 B4 B5

B6 B7

mM NaCl

50

1000

0 20 40 60 80 100 120 140

Buffer Volume (mL)

1400

1200

1000

800

600

400

200

0

mAU

• First GH7 identified in an animal

• Major protein in the digest tract

• Shows both cellobiohydrolase

and endoglucanase activity

Research Highlight

Visit Renewall.eu www.renewall.eu

www.sunlibb.eu

Blue biotechnology is a term that has been used to describe the

marine applications of biotechnology.

Green biotechnology is biotechnology applied to agricultural

processes.

Red biotechnology is applied to medical processes, e.g. design of

organisms to produce antibiotics.

White biotechnology, also known as industrial biotechnology is

biotechnology applied to industrial processes. An example is the

designing of an organism to produce a useful chemical…or the

using of enzymes as industrial catalysts.

What is Industrial Biotechnology Exactly?

http://en.wikipedia.org/wiki/Biotechnology

“Industrial Biotechnology (IB) is a set of cross-disciplinary technologies that

use biological resources for producing and processing materials and chemicals

for non-food applications. These resources can be derived from the tissues,

enzymes and genes of plants, algae, marine life, fungi and micro-organisms.”

http://www.bbsrc.ac.uk/funding/priorities/ibb-industrial-biotechnology.aspx

Astbury Centre for

Structural Molecular Biology

Industrial biotechnology: An example

• Directed evolution of synthetically-useful catalytic function

• Novel structural insights into enzyme catalysis and control

• Other academics in the Astbury Centre with interests in directed evolution of enzyme function include Mike McPherson

O

OH

CO2HOH

HO

Pr2N

O

Directed

evolution

Understand new

functions

Berry, Pearson and Nelson, J. Mol. Biol. 2010, 404, 56

• Novel substrates / products e.g. fluorinated

• Novel stereochemistry

Berry and Nelson, J. Am. Chem. Soc. 2006, 128, 16238

Industrial biotechnology: For example, to modify enzyme stereochemistry

Astbury Centre for

Structural Molecular Biology

IgG1 Monoclonal Antibody

P Intron LC Intron

P CMV PolyA P CMV PolyA Psv SVintron/PolyA

P P GS

Ori Amp

Light chain Heavy chain Glutamine

HC P Intron LC Intron

P CMV PolyA P CMV Psv

P P GS

Ori Amp

synthetase

HC

1

2

Industrial Biotechnology is Built

Upon Core Bioscience

Operating in an Industrial,

Engineered Environment

Productivity

Module

Product Quality

Module

Cell Growth/Response

Module

Microscale

Process

Simulation

Cell/product

analytics

Key parameter

constraints for

mathematical

modelling

Mathematical Modelling

Environment

Whole Process

Cell Engineering

in silico

Prediction of

productivity/

product quality

constraint

combinations

CHO Cell

BioBrick

Repository

Bespoke

vector

construction

Cell Factory Design Based on Engineering Principles

Cell

engineering

Selection of

CHO cell

functional

effectors

A Paradigm for Synthetic Bioengineering of

the Mammalian Cell Factory

Engineering and Bioscience Must Work in Synergy

or Merge into a new “Biological Engineering”

The Impact of Engineering on Biotechnology

A Fluidic Oscillator Making Microbubbles!

• 20 micron sized bubbles from 20 micron sized pores

• Rise / injection rates of 10-4 to 10-1 m/s without coalescence: uniform spacing/size

• Watch the videos!

Same Diffuser

Prof Will Zimmerman, University of Sheffield

Two trials were carried out with Dunaliella salina using power plant exhaust gas as

the carbon source. Second trial was run for three weeks with improved operating

conditions compared to the first trail, which was only run for two weeks.

0.00%

500.00%

1000.00%

1500.00%

2000.00%

2500.00%

3000.00%

3500.00%

4000.00%

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Time (d)

Dry

bio

ma

ss %

in

crea

se

Field trial 2 Field trial 1

Inlet and outlet CO2 and O2

concentrations were measured

by FTIR. The difference

between red curves shows CO2

uptake while the difference

between blue curves shows O2

stripping rate.

Supra-exponential growth

Thanks to:

Simon McQueen-Mason - York

Adam Nelson - Leeds

Will Zimmerman - Sheffield

a brief introduction of what the BBSRC’s strategic theme of ‘Bioenergy and

Industrial Biotechnology’ is, how the WR Universities deliver research which fits

into this theme and how this benefits the students in the DTP.