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BIOSECURITY TOOL TO DETECT GENETICALLY ENGINEERED ORGANISMS IN WILD MICROBE-GROWN HEADPHONES UNVEILED IN FINLAND OFFERS GLIMPSE OF RENEWABLE FUTURE SYNTHETIC BIOLOGY START-UP RECEIVES PRIVATE EQUITY INVESTMENT BOOST BRINGING SYNTHETIC BIOLOGY INNOVATIONS TO COMMERCIAL SCALE

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Page 1: BRINGING SYNTHETIC BIOLOGY INNOVATIONS TO ... - Bio Market …€¦ · “A great opportunity to learn about companies and organisations across the whole value chain, with many opportunities

BIOSECURITY TOOL TO DETECT GENETICALLY ENGINEERED ORGANISMS IN WILD

MICROBE-GROWN HEADPHONES UNVEILED IN FINLAND OFFERS GLIMPSE OF RENEWABLE FUTURE

SYNTHETIC BIOLOGY START-UP RECEIVES PRIVATE EQUITY INVESTMENT BOOST

BRINGING SYNTHETIC BIOLOGY INNOVATIONS TO COMMERCIAL SCALE

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www.synbiomarkets.com

18 - 19 November 2019 | Ewerk, Berlin, Germany

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PARTNERS, SPONSORS AND EXHIBITORS

PRESENTATIONS, PANELS AND ROUNDTABLES

DECISION MAKERS IN ATTENDANCE

ONE-TO-ONE PARTNERING MEETINGS

“A great opportunity to learn about companies and organisations across the whole value chain, with many opportunities to engage with speakers during the panel discussions and networking breaks. The organisers provided a ready mechanism and rooms for scheduling individual meetings that were productive with so many thought-leaders and decision-makers in attendance.”Steve Cohen, Director of Catalyst and Chemical Technology, Elevance Renewable Sciences

CONNECTING SYNBIO INNOVATION TO COMMERCIAL END MARKETS

INDUSTRY LEADING SPEAKERS

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CONTENTS02Editor’s Welcome.

03Researcher conducts gene-editing experiments on sugarcane.

05Lab-grown headphones made from fungus unveiled in Finland.

07Plastic-digesting enzyme produced to help bio-recycling loop.

09Synthetic biology start-up receives private equity investment boost.

10Zymergen teams up with Sumitomo to drive development of new materials.

11Drug-producing bacteria engineered using synthetic biology.

13Synthetic biology used to target cancer cells while sparing healthy tissue.

15Biosecurity tool to detect engineered organisms in wild.

CLICK ON TITLE TO GO TO ARTICLE

EDITOR & CO-FOUNDER:Luke [email protected]@Bio_Markets

CHIEF EXECUTIVE OFFICER & CO-FOUNDER:Alex [email protected]@alexjwmedia

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GLOBAL SALES DIRECTOR:Matt [email protected]

COMMERICAL MANAGER:Ryan [email protected]

DEPUTY EDITOR:Liz [email protected]@LizGyekye

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Bio-Based World Limited WeWork, 131 Finsbury PavementLondon, United KingdomEC2A 1NT

Bio Market Insights Reports are Designed by Coterie Creative Ltdwww.coteriecreative.co.uk

Bio Markets Insights Reports are Published by Bio-Based WorldNews Ltd.

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SYNTHETIC BIOLOGY REPORT – JUNE 2019 1

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EDITOR’S WELCOMEHumans have been using biology to their own purposes for thousands of years. They have reshaped livestock through selective breeding and reshaped crops.

Throughout the last half of the 19th century and the first years of the 20th, scientific research has changed the world and continues to transform many lives. From 1996 onwards, we have seen ‘Dolly the sheep’, the first mammal cloned from an adult cell, seen stem cells analysed and the introduction of CRISPR.

Today, this research has led to a new interdisciplinary area making waves - synthetic biology.

Synthetic biology involves redesigning organisms for useful purposes by engineering them to have new abilities. This exciting area is worth covering as it has become increasingly prevalent in the modern world and this is why Bio Market Insights has focused our second report on this topic.

According to the United Nations, the world’s population will grow to around 8.5 billion in 2030. At the moment, it stands at 6.5 billion. This will mean more people using more energy and water. So, there will be a real urgency to use all the tools at our disposal to help with these challenges. Synthetic biology can play a vital role here. By engineering organisms for new purposes, scientists can produce new food, fuels, drugs and chemicals for beneficial reasons.

In fact, synthetic biology researchers and companies around the world are already harnessing the power of nature to solve problems in medicine, manufacturing and agriculture. And, a number of companies have successfully brought their synthetic biology innovations to commercial scale, which we cover in this report.

“By learning about how cells operate and testing the constraints under which they evolve, we can come up with ways

of engineering cells more efficiently for a wide range of applications in biotechnology,” says José Jiménez, Lecturer in Synthetic Biology at the University of Surrey’s Faculty of Health and Medical Sciences, in this report.

Nevertheless, there are valid arguments against this technology, ethical dilemmas and an element of risk. What happens if you manufacture an organism which damages the environment or manufacture an organism that is in itself dangerous? These are hypothetical arguments at the moment, but ones that need addressing.

Scientists are already working on assuaging these fears. For example, some are developing biosecurity tools that can detect genetically or synthetically engineered microorganisms based on their unique DNA signatures in the wild (see page 15).

We need to talk about synthetic biology. This discussion must involve scientists, companies, ethicists and policymakers, but also wider society. The science world should carry people with them as this new field develops. We also want to inform the bio-based world about this interdisciplinary development.

This focus on the commercial development of synthetic biology is at the heart of our next conference ‘SynBio Markets’ coming to Berlin in November.

I hope you enjoy this latest report. Please see our full editorial calendar on the last page of this guide and if you wish to contribute to a future edition, or suggest a new topic, feel free to contact me.

Thanks for reading!

Liz GyekyeDeputy Editor at Bio Market [email protected] @LizGyekye

“BY LEARNING ABOUT HOW CELLS OPERATE AND TESTING THE CONSTRAINTS UNDER WHICH THEY EVOLVE, WE CAN COME UP WITH WAYS OF ENGINEERING CELLS MORE EFFICIENTLY FOR A WIDE RANGE OF APPLICATIONS IN BIOTECHNOLOGY.”

2SYNTHETIC BIOLOGY REPORT – JUNE 2019

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AUSTRALIAN SCIENTIST CONDUCTS GENE-EDITING EXPERIMENTS ON SUGARCANE IN

ORDER TO PRODUCE BIO-PRODUCTS.

An Australian researcher is conducting gene-editing experiments to tailor sugarcane production to effectively produce biofuels and bioplastics. Professor Robert Henry, Director of the Queensland Alliance for Agriculture and Food University (QAAFI) at the University of Queensland, said sugarcane’s “reinvention” as an “energycane” crop could sustain the industry in the face of falling global demand for sugar.

“The industry must think beyond just producing sugar, to also

producing electricity, biofuels for transportation and oils to

replace traditional plastics,” he said.

He added: “It’s about reinventing sugarcane as a crop with a

wider range of end uses, and sugarcane is ideal for renewables

because it is fast-growing with abundant biomass.”

He is working with a global team to sequence the

sugarcane genome as part of a US Joint Genome Institute

project. “Sugar is the last major cultivated plant to have its

genome sequenced, and we expect to see it fully decoded

by 2020,” Henry.

“Having sugar’s genetic template will allow us to look at

growing sugarcane as a biofuel and a source of 100%

recyclable bioplastic, making it a substitute for petroleum in

the production of countless items from cosmetics to car parts,”

he added.

Professor Henry’s call to revamp sugarcane is supported

by Cooperative Research Centre for Developing Northern

Australia Chair Sheriden Morris.

She said: “Gene-editing of the sugarcane genome will allow

the sugar industry to explore adaptations that will reduce

environmental impacts, especially on the Great Barrier Reef. It

will help the industry to broaden the potential of a sugar crop

to a wider range of uses.

“Biofuels and bioplastics will be important to the long-term

future of the industry.”

SUGAR IS THE LAST MAJOR CULTIVATED PLANT TO HAVE ITS

GENOME SEQUENCED, AND WE EXPECT TO SEE IT FULLY DECODED BY 2020.”

SYNTHETIC BIOLOGY REPORT – JUNE 2019 3

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AUSTRALIAN SCIENTIST CONDUCTS GENE-EDITING EXPERIMENTS ON SUGARCANE IN

ORDER TO PRODUCE BIO-PRODUCTS. (CONT.)

‘A RANGE OF VARIETIES’

Henry, who has helped lead genomic breakthroughs in

decoding the sugarcane genome, said the science was quickly

developing to allow growers to tap into the commercial

opportunities in renewables.

“Australia’s sugarcane growers are facing a falling sugar

price – driven by declining world demand and increased

competition in India and Brazil. The industry must look to the

future,” Henry said.

QAAFI researchers supported by the US Joint BioEnergy

Institute and Sugar Research Australia grant are testing a range

of sugarcane varieties to identify which types produce ethanol

most effectively and efficiently.

Researchers are also collaborating with the Indian Institute

of Technology in Delhi to investigate to processes that break

down sugarcane fibre to make bioplastics.

“Drink bottles made from sugarcane bioplastics are just

one product on the agenda from this collaboration,” Henry

explained. “Economics is key. Now that we understand more

about the genetics of sugarcane, these sorts of products are

becoming commercially realistic.”

Elsewhere, researchers from Michigan State University have

developed synthetic biology tools to co-produce high-value

compounds in plants, according to a study published in the

journal Nature Communications.

Terpenoids from the largest class of natural products in plants

have been used by humans for thousands of years, according

to the US researchers. Modern applications for terpenoids

range wide, from pharmaceuticals, fragrances, nutraceuticals,

biopesticides to chemical feedstocks.

However, in the context of industrial scale production,

plant accumulations of terpenoids is rather low. And, in the

pursuit to extract natural terpenoids, some wild plant species

have even become endangered, Michigan State University

researchers said.

Radin Sadre, Synthetic Biologist/Biochemist in the Department

of Horticulture, said: “We investigated novel strategies to

sustainably produce high-value terpenoid biomaterials in plants.”

Sadre is the lead author of the study conceived by Christoph

Benning, MSU-DOE Plant Research Laboratory director and

Bjoern Hamberger, Assistant Professor in the Department of

Biochemistry and Molecular Biology.

SYNTHETIC BIOLOGY REPORT – JUNE 2019 4

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LAB-GROWN HEADPHONES MADE FROM FUNGUS AND BIOPLASTIC UNVEILED IN FINLAND

Finnish design and innovation company Aivan has created a pair of headphones made exclusively from microbially-grown materials. The ‘Korvaa’ headset was produced to showcase the potential of synthetic biology in the form of a three-dimensional object.

Aivan teamed up with synbio scientists from the VTT Technical

Research Center of Finland and Aalto University to develop the

necessary components for the headset.

Traditionally, headphones are normally made from fossil fuel-

based plastic and contain a variety of hard and soft materials

that are usually not biodegradable. Aivan’s headphones feature

six different microbially-grown substances, including fungus

and yeast-based bioplastic.

The primary structure of the headphones is 3D-printed and

uses a bioplastic created with lactic acid produced by yeast.

The polylactic acid polymer is durable and flexible enough to

form the body. According to Aivan, in the future, this bioplastic

could be produced using CO2 as feedstock.

Padded earpieces were created from a protein called

hydrophobin that is made up of many tiny bubbles, resembling

artificial foam. The earbuds are covered in mycelium, which

is a fungus-derived material for flexibility to cover the ear

cuffs. The mesh on the Korvaa headphones is created by

spinning out synthetic spider silk. The Korvaa headphone is a

non-working prototype right now. Aivan stated that the main

objective of the initiative was to show that electronics do not

need to be made from non-biodegradable materials.

Saku Sysiö, Head of Product Design and Co-founder at Aivan,

told Bio Market Insights that these microbially-grown materials

could replace some fossil fuel-based plastics in the future.

He said that the change would probably happen in high-end

products first “because of the higher cost of production, and

then become the ‘norm’”.

Sysiö added: “The research is still in the early stages, and when

the development pushes ahead we’ll see lots of new materials

with more and more improved properties. In addition to this,

we will have better control over them. The field of synthetic

biology has taken leaps in the past ten years – something that

used to take a year, we can now do in a matter of days. I think

this trend will keep on going.”

THE PRIMARY STRUCTURE OF THE HEADPHONES IS 3D-PRINTED AND

USES A BIOPLASTIC CREATED WITH LACTIC ACID PRODUCED BY YEAST. THE POLYLACTIC ACID POLYMER IS DURABLE AND FLEXIBLE ENOUGH TO FORM THE BODY. ACCORDING TO AIVAN, IN THE FUTURE, THIS BIOPLASTIC COULD BE PRODUCED USING CO2 AS FEEDSTOCK.”

SYNTHETIC BIOLOGY REPORT – JUNE 2019 5

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LAB-GROWN HEADPHONES MADE FROM FUNGUS AND BIOPLASTIC UNVEILED IN FINLAND (CONT.)

This project enabled an important collaboration between

applied sciences and industrial design. During the process,

valuable insight into the properties of these new materials

was obtained. Sysiö said that the project did not stem from a

business plan and the designers “got to work with materials

that had no relatable prior use-case scenarios”, adding: “we

rarely get this type of insight into the science behind the

materials we work with, or get to be a part of the development

in such close collaboration with scientists”.

Sysiö added: “Understanding materials and production methods is

a part of any product designers key-competence, and these days

we have to factor in circularity as well. In that sense we probably

have gained a better understanding of, for instance, bioplastics in

general, compared to the average consumer. But we’re learning

about new things every day and that makes us hyper-sensitive.

“We understand that the more this field develops, the bigger

the risk that all current attempts at eco-friendliness will look

inadequate, or — worst case scenario — like greenwashing

efforts, in the near future. But as designers, it’s in our nature to

keep an open mind towards these things. We will always see the

future as full of possibilities.”

All in all, the Korvaa project aimed to raise awareness and

highlight the potential opportunities in synthetic biology. Sysiö

said that the initiative “far exceeded any expectations any of

the scientists, artists or designers involved in the project had”.

Sysiö explained: “It’s not about the depletion of fossil raw

materials, but the shift in buying behaviour. ‘Stuff’ needs to have

a purpose and actions need to make a difference. Korvaa should,

at the very least, be proof to any consumer electronics brand (or

any other brand for that matter) that the market is thirsty for bio-

based products, going beyond plastic straws and bags.”

“This was certainly only a surface scratch into where biology-

engineered materials are going, and what we can do with them

in the future. For now, we were able to showcase two versions

of the Korvaa headset; the current material composition, and

the target for the future,” said Thomas Tallqvist, Industrial

Designer at Aivan.

The headphones will be on display at several design shows in

Finland in September.

SYNTHETIC BIOLOGY REPORT – JUNE 2019 6

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RESEARCHERS PRODUCE ENZYMES WHICH COULD CREATE ‘PERFECT’

BIO-RECYCLING LOOP FOR PLASTICS

A Germany-based research team has been able to produce enzymes which can break down PET plastics and other polymers into their basic building blocks.

The researchers from the University of Greifswald and

Hemholtz-Zentrum-Berlin (HZB) have figured out the 3D

structure of a plastic-digesting enzyme called MHETase.

MHETase can be used in combination with a second enzyme,

PETase, to break PET plastic into its basic components, which

can then be used to produce new plastic.

According to the researchers, applying these enzymes could

create a “perfect” bio-recycling loop for plastics – allowing

them to be broken down and reprocessed without waste – and

cutting out the need for crude oil to produce virgin materials.

The HZB research, recently published in journal Nature

Communications, forms the final piece of a puzzle that

researchers have been working to solve since 2016 – when

Japanese scientists identified a bacteria that lives on and

partially digests PET using PETase and MHETase.

In the following two years, research teams around the world

raced to replicate the structure of the enzymes. Last year,

the structure of PETase, the more simple of the two, was

discovered independently by teams in Korea, China, UK, US

and Brazil, reflecting the high level of international interest.

MEHTase, which completes the decomposition process started

by PETase, proved more difficult to crack. According to HZB

researcher Dr Gert Weber, a single MHETase molecule consists

of 600 amino acids, or about 4000 atoms. But he added that it

had a great potential to optimise plastic bio-recycling.

Weber said: “MHETase has a surface that is about twice as large

as the surface of PETase and has therefore considerably more

potential to optimise it for decomposition of PET.”

Weber and biotechnologist Professor Uwe Bornscheuer

approached the problem by studying how the enzyme bound

to MHET – a smaller building block of PET that is produced by

plastic digested by PETase.

BACK TO BASICS

In a statement, Weber said that to break down these smaller

building blocks into PET’s basic components, the enzyme first

needs to “dock” them in a tailor-made 3D structure.

“We can now exactly localise where the MHET molecule docks

to MHETase and how MHET is then split into its two building

blocks: terephthalic acid and ethylene glycol,” Weber added,

explaining that the BESSY II synchrotron was used to produce

extremely bright X-rays that shed light on the complex

structure.

Weber said: “In order to see how MHETase binds to PET and

decomposes it, you need a fragment of plastic that binds to

MHETase but is not cleaved by it.”

A member of Weber’s prior research team in Greifswald, Dr.

Gottfried Palm, cut up a PET bottle, chemically decomposed

the PET polymer and synthesised a small chemical fragment

from it that binds to MHETase but can no longer be cleaved by

it. From this ‘blocked’ MHETase, tiny crystals were grown for

structural investigations at the HZB.

According to the researchers, neither PETases nor MHETase are

particularly efficient yet.

“Plastics have only been around on this scale for a few

decades; even bacteria with their rapid successions of

generations and rapid adaptability have not managed to

develop a perfect solution through the evolutionary process of

trial and error over such a short time,” he explained.

Weber’s team is working to accelerate the process. They have

used their 3D structure to create a new version of MHETase

that was able to digest MHET and another PET building block,

BHET, more efficiently than the natural enzyme.

The enzyme MHETase is a large complex folded molecule. MHET molecules from PET plastic dock on to MHETase at certain locations and are then split into their building blocks. © Martin Künsting

SYNTHETIC BIOLOGY REPORT – JUNE 2019 7

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SYNTHETIC BIOLOGY START-UP RECEIVES PRIVATE EQUITY INVESTMENT BOOST

UK-based synthetic biology company Zentraxa has received £113k investment from a private equity firm to take its business to the next stage of development.

The Bristol Private Equity Club (BPEC) has invested £113k of

the £500k that Zentraxa, a University of Bristol spin out biotech

company, requires to take the fledgling business to the next

stage of development.

Zentraxa was formed in 2017 and is commercialising Zentide, a

unique manufacturing process to produce biological adhesives

for use in sectors including healthcare.

Zentraxa is already in partnership talks with a global

healthcare company and now wants to take its products and

manufacturing processes past the feasibility stage and start

testing them in the real world.

“We’re developing both a manufacturing process and our own

biomaterials that are highly effective adhesives. Both these

technologies are based on processes found in the natural

environment, making it more environmentally-friendly and

sustainable than other petrochemical-derived products currently

being used,” said Martin Challand, Chief Technology Officer at

Zentraxa. “With investment in place, the focus for the coming

months will be optimisation of our Zentide process from lab

to pilot scale, which will allow more accurate product costing,

providing improved business focus and customer traction.”

After announcing they were looking for a £500k investment

to allow continuation of their development work, Martin and

his team were introduced to BPEC, which is made up of 80

business experts and entrepreneurs keen to work with Bristol

technology firms and help them thrive and grow.

‘AMBITIOUS VISION’

Jerry Barnes, one of BPEC’s founding members, said: “We are

always looking for investment opportunities with innovative

Bristol-based businesses with the potential for rapid scale-up

and Zentraxa is a perfect example of that.

“Even though Martin and his team come from a scientific,

rather than business, background they have proven themselves

to be gifted entrepreneurs with an ambitious vision to make

take their product to the global marketplace.”

In six months to 31 March 2019, BPEC invested £1m in seven

deals, including Zentraxa. In three years BPEC has invested a

total of £4.6m in 14 Bristol-based businesses and has seen its

own membership swell from 49 members in 2016 to 80 today.

“We see lots of applications for our biological adhesive

products,” said Challand. “We are initially focusing on the

healthcare sector and applications such as wound dressing

where our biologically-derived adhesives show many benefits

sticking materials to skin.

“But, as we progress, there are lots of possibilities, especially

as more and more industries look towards environmentally-

sustainable solutions like ours.” He added: “This is a crucial

stage in our development and we are delighted to have the

Bristol Private Equity Club on board as we progress past the

feasibility stage and onto proving that our technology can be a

global leader.”

Barnes explained: “Bristol has an excellent eco-system for

tech-minded start-ups and university spin-offs with truly

world-class businesses being produced.

“We are always keen to hear from the city’s technology

entrepreneurs to see if there is any way we can provide the

investment they need to scale up and take their businesses to

the next level.”

WE ARE INITIALLY FOCUSING ON THE HEALTHCARE SECTOR AND

APPLICATIONS SUCH AS WOUND DRESSING WHERE OUR BIOLOGICALLY DERIVED ADHESIVES SHOW MANY BENEFITS STICKING MATERIALS TO SKIN.”

SYNTHETIC BIOLOGY REPORT – JUNE 2019 9

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ZYMERGEN TEAMS UP WITH SUMITOMO TO DRIVE DEVELOPMENT OF NEW MATERIALS

Japanese chemical company Sumitomo Chemical and US synthetic biology specialist Zymergen have signed a multi-year partnership to bring new specialty materials to the market. This collaboration between the two companies will enable the development of new materials to meet consumer trends in high-tech industries.

Today, electronics makers and consumers seek devices that

are lighter, smaller, more battery efficient, have optimised

displays, and new functionality– all at a lower cost. Electronics

manufacturers are increasingly demanding next-generation

materials for these next-generation electronics because the

current petrochemical toolbox is limited, expensive, and

difficult to manufacture.

In order to better meet these demands, Sumitomo Chemical

has decided to partner with Zymergen, whose mission is to

build a sustainable future through biology, to discover novel

and improved molecules to bring to market competitive, high-

performance, specialty materials to better serve the electronics

industry and more. This partnership will leverage Zymergen’s

proprietary platform which combines advances in artificial

intelligence, robotic lab automation, and cutting-edge genomics,

to unlock previously inaccessible sources of molecular diversity

based on sustainable and renewable resources. Sumitomo

Chemical is a well-known supplier to major electronics

companies, with approximately 20% of the company’s sales

revenue in IT-related chemicals. The company’s industry insight

will ensure that materials meet application requirements that

will drive the next generation of electronics products. According

to Sumitomo, it will bring access to key markets, a reputation

for quality and excellence, and the applications knowledge to

connect new materials to the best products.

Sumitomo Chemical and Zymergen will develop specialty

materials that may include optical films for displays, hard

coatings that will not scratch, flexible electronics circuits and

adhesive materials. These new materials can help make next-

generation, high tech products a reality for consumers.

Richard Pieters, President of Zymergen’s products business,

said he saw the partnership as an opportunity to drive real

innovation in the consumer electronics space. He added: “This

cooperation unites the best of both worlds with Zymergen’s

expertise exploring the molecular diversity of biology to

make new polymers and materials, and Sumitomo Chemical’s

technology leadership in serving the most demanding markets

and unique insights in next-generation materials.”

“Partnering with Zymergen combines our chemical technologies

with their expertise in molecular diversity of biology that will allow

us to develop high-performance materials to meet customer

demand,” said Hiroshi Ueda, Vice President at Sumitomo

Chemical. “Through molecular biology we will be able to deliver

our customers performance capabilities not previously possible

by reliably and cost-effectively engineering biology.” Together,

Sumitomo Chemical and Zymergen will work to develop new

and unique materials, making the impossible possible for the

electronics industry and beyond, according to both companies.

Richard Pieters, President of Zymergen’s products business,

is a speaker at SynBio Markets 2019.

SYNTHETIC BIOLOGY REPORT – JUNE 2019 10

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DRUG-PRODUCING BACTERIA ENGINEERED USING SYNTHETIC BIOLOGY

Bacteria could be programmed to efficiently produce drugs, thanks to breakthrough research into synthetic biology using engineering principles from UK-based universities.

Led by the Warwick Integrative Synthetic Biology Centre at

Warwick’s School of Engineering and the Faculty of Health

and Medical Sciences at the University of Surrey, new research

has discovered how to dynamically manage the allocation

of essential resources inside engineered cells – advancing

the potential of synthetically programming cells to combat

diseases and produce new drugs.

The researchers have developed a way to efficiently control

the distribution of ribosomes – microscopic ‘factories’ inside

cells that build proteins that keep the cell alive and functional

– to both the synthetic circuit and the host cell.

Synthetic circuitry is added to the host cells to enhance the

performance of the cell to produce desired proteins. Adding

synthetic circuitry will enable the cell to be used as a factory to

produce antibiotics and other valuable drugs. This will create

great potentials in healthcare and pharmaceuticals.

When the synthetic circuitry is added to the host cell, they both

compete for the resources produced by the ribosome as the

number of ribosome in the cell is finite.

The researchers have demonstrated how ribosomes can

be distributed dynamically, using engineering principle of

feedback loop which is used in aircraft flight control system,

this will help in allocating ribosomes to the synthetic circuit

when it requires and less to the host cell and vice versa.

TACKLING IMPORTANT CHALLENGES

Declan Bates, Professor of Bioengineering at the University of

Warwick’s School of Engineering and Co-Director, Warwick

Integrative Synthetic Biology Centre (WISB), said: “Synthetic

biology is about making cells easier to engineer so that we

can address many of the most important challenges facing

us today – from manufacturing new drugs and therapies to

finding new biofuels and materials.

SYNTHETIC BIOLOGY IS ABOUT MAKING CELLS EASIER TO

ENGINEER SO THAT WE CAN ADDRESS MANY OF THE MOST IMPORTANT CHALLENGES FACING US TODAY – FROM MANUFACTURING NEW DRUGS AND THERAPIES TO FINDING NEW BIOFUELS AND MATERIALS.”

SYNTHETIC BIOLOGY REPORT – JUNE 2019 11

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DRUG-PRODUCING BACTERIA ENGINEERED USING SYNTHETIC BIOLOGY (CONT.)

He added: “It’s been hugely exciting in this project to see an

engineering idea, developed on a computer, being built in a lab

and working inside a living cell.”

José Jiménez, Lecturer in Synthetic Biology at the University

of Surrey’s Faculty of Health and Medical Sciences, said: “The

ultimate goal of the selective manipulation of cellular functions

like the one carried out in this project is to understand

fundamental principles of biology itself.

By learning about how cells operate and testing the

constraints under which they evolve, we can come up with

ways of engineering cells more efficiently for a wide range of

applications in biotechnology.

“Ribosomes live inside cells, and construct proteins when

required for a cellular function. When a cell needs protein, the

nucleus creates mRNA, which is sent to the ribosomes – which

then synthesise the essential proteins by bonding the correct

amino acids together in a chain.”

The topic of synthetic biology is gaining ground across the

globe. In May of this year, scientific institutions from countries

across the globe came together to launch a new alliance to

help develop synthetic biology.

The Global Alliance of Biofoundries (GBA) brings together

16 institutions from countries including the UK, US, Japan,

Singapore, China, Australia, Denmark and Canada.

The London DNA Foundry, based at Imperial College London,

is one of the leading founders of the new Global Alliance.

The GBA will share knowledge, infrastructure and expertise

to tackle global challenges and play a central role in

the ‘synthetic biology revolution’ and the transition to a

new global bio-based economy. Biofoundries are being

established at universities and institutions around the world to

provide the infrastructure and technology to both accelerate

academic research and develop the new synthetic biology

industry. Examples of research include manufacturing new

vaccines and developing living therapeutics, designing and

building DNA, creating biofuels, and making bioplastics more

effectively and sustainably.

Professor Paul Freemont, Co-Director of the London DNA

Foundry based at Imperial, said: “The Global Alliance of

Biofoundries is a major step to accelerating the synthetic

biology industry worldwide.

“It will provide researchers around the globe with the tools and

technologies to exploit fundamental research and will support

new industries to develop. “Modern biology will be led by these

foundries which will benefit society and drive the transition to

a global bioeconomy.” Professor Richard Kitney, Co-Director

of the UK Innovation and Knowledge Centre for Synthetic

Biology, SynbiCITE said: “Synthetic biology is one of the most

exciting and rapidly growing scientific areas.

“The last five years has seen a number of biofoundries set

up around the world and this new Alliance will bring them

together to collaborate and tackle global challenges.”

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SYNTHETIC BIOLOGY USED TO TARGET CANCER CELLS WHILE

SPARING HEALTHY TISSUE

A synthetic protein has demonstrated the ability to kill cancer cells whilst sparing healthy ones, according to a recent study from US-based Stanford University School of Medicine.

Some types of cancers are caused by mutated or

overexpressed cell surface proteins that signal to the nucleus

to drive uncontrolled growth and survival, according to the

researchers. However, the researchers say that they have been

able to use an approach called RASER (rewiring of aberrant

signaling to effector release) to ensure that cancer-causing

signals are redirected away from cell growth and survival and

toward programmed cell death.

According to the researchers, RASER relies on only two

proteins. The first is activated in the presence of an “always

on” growth signal often found in cancer cells, and the second

carries out a researcher-programmed response, such as

triggering the expression of genes involved in cell death.

Although the experiments were confined to cells grown in the

laboratory, the researchers believe the results could lead to a

new type of cancer therapy in which synthetic proteins deliver

highly targeted and customisable treatments to sidestep the

sometimes devastating side effects of current options.

“We’re effectively rewiring the cancer cells to bring about

an outcome of our choosing,” said Michael Lin, MD, PhD,

Associate Professor of neurobiology and of bioengineering.

“We’ve always searched for a way to kill cancer cells but not

normal cells. Cancer cells arise from faulty signals that allow

them to grow inappropriately, so we’ve hacked into cancer

cells to redirect these faulty signals to something useful.”

A paper describing the work was published 2 May in journal

Science. Lin is the senior author. Former graduate student

Hokyung Chung, PhD, is the lead author.

BACKGROUND

Many cancers rely on a series of signals that originate from

proteins called receptors that span the membrane of the cell.

These signaling cascades, or pathways, are used by healthy

cells to grow in response to external cues, for example during

development or recovery from injury. Often, however, these

receptor proteins are mutated or overexpressed in cancer cells

in ways that render the receptor protein “always on”, providing

the cell with constant, unwarranted signals for growth.

The researchers focused on two receptors, EGFR and

HER2—members of a family of receptors called the ErbB

receptors—that often drive the growth of brain, lung and

breast cancers. These are often the target of many common

anti-cancer drugs.

Stanford researchers have developed synthetic proteins that can rewire cancer cells in a lab dish. © Stanford University School of Medicine

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Many common anti-cancer drugs, including Herceptin, work

by blocking the cascade of signals triggered by receptor

activation. Receptor targeting drugs, such as Herceptin for

breast cancer, are effective at blocking the growth signals,

though lack the ability to discriminate between cancerous and

non-cancerous cells, resulting in the death of both cells alike.

That’s where Lin and his team come in.

“We haven’t had a drug that can tell the difference between a

pathway signaling normally and one that is abnormally active,” Lin

said. “We knew we needed a better strategy, a more rational way

of treating cancer. But we’ve not had a way to do it until recently.”

To overcome this issue, the group used RASER.

Chung and her colleagues designed a synthetic protein

consisting of two natural proteins fused together—one that

binds to active ErbB receptors and another that cleaves a

specific amino acid sequence. They then engineered a second

protein that binds to the inner surface of the cell membrane

and contains a customisable “cargo” sequence that can carry

out specific actions in the cell. When the first protein binds to

an active ErbB receptor, it cuts the second protein and releases

the cargo into the interior of the cell.

“When the receptor protein is always on, as it is in cancer cells,

the released cargo protein accumulates over time,” Chung

said. “Eventually enough accumulates to have an effect on the

cell. In this way, the system produces an effect only in cancer

cells, and we can convert the always-on state of the receptor

into different outcomes through the choice of cargo protein.”

After several rounds of tinkering, the team saw that their RASER

system was highly specific for cancer cells dependent on ErbB

receptor activity. For their first test they chose to use a protein

involved in triggering cell death as the RASER cargo.

The team compared the RASER system to two currently used

breast cancer therapies, chemotherapy and an ErbB inhibitor,

on a variety of in vitro cultured breast and lung cell types;

cancerous with overactive ErbB, cancerous with normal ErbB

activity and non-cancerous.

They found that, of the treatments tested, only RASER

demonstrated specificity in killing cells with an overactive

ErbB pathway. The traditional chemotherapy regime killed

cells indiscriminately and the effect of the ErbB inhibitor varied

though showed no correlation to pathway activity levels.

Currently, the RASER approach has only been demonstrated on

cell culture and more work is needed to determine its viability

as a treatment for human tumours in vivo. However, the team

remain excited about the possible applications of the system,

utilising its customisability to recognise other mutated receptors

and using different cargos to achieve different results.

Lin said he was optimistic about future studies, adding: “We

have so much more information now about cancer genomics,

signaling and how cancer cells interact with the immune system.

It’s finally becoming practical to combine this knowledge with

synthetic biology approaches to tackle some of these pressing

human health problems. RASER is both customisable and

generalisable, and it allows us for the first time to selectively

target cancer cells while sparing normal signaling pathways.”

SYNTHETIC BIOLOGY USED TO TARGET CANCER CELLS WHILE

SPARING HEALTHY TISSUE (CONT.)

RASER IS BOTH CUSTOMISABLE AND GENERALISABLE, AND IT

ALLOWS US FOR THE FIRST TIME TO SELECTIVELY TARGET CANCER CELLS WHILE SPARING NORMAL SIGNALING PATHWAYS”

SYNTHETIC BIOLOGY REPORT – JUNE 2019 14

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BIOSECURITY TOOL TO DETECT ENGINEERED ORGANISMS IN WILD

If a synthetically or genetically engineered organism is released into the environment, how will we know? This is a question trying to be answered by a multi-institution research team from US Worcester Polytechnic Institute (WPI). The team, led by Eric Young, assistant professor of chemical engineering at WPI, is developing a biosecurity tool that can detect genetically or synthetically engineered microorganisms based on their unique DNA signatures.

The tool can identify engineered organisms when they are

mixed in with a myriad of naturally occurring microorganisms,

WPI said in a statement. It can also be used to protect a

company’s intellectual property should an organism it

designed accidentally escape the lab or to detect intentional

releases of potentially harmful organisms.

The DNA signature tool project is funded by an 18-month

award from the Finding Engineering Linked Indicators (FELIX)

programme, which is run through Intelligence Advanced

Research Projects Activity (IARPA), an organisation within the US’

Office of the Director of National Intelligence that funds research

to address challenges facing the US intelligence community.

The award has a second phase that could be renewed for

an additional 24 months. Raytheon, a Massachusetts-based

defense contractor, is the primary contractor; Young, who has

received a $377,746 award for his part of the project, is one of

five subcontractors. The others are Johns Hopkins University,

Princeton University, University of California at San Francisco, and

Mission Bio, a San Francisco-based biotech company.

“We realise the power of engineering and bioengineering,”

said Young, whose expertise is in synthetic biology, including

the genetic engineering of bacteria, yeast, and fungi. “We are

excited about the promise of synthetic biology, but we also

have an ethical responsibility to think about the potentially

negative uses of the technologies we develop.

“My lab is developing engineered organisms to solve problems,

and we use safety practices beyond what we are required to use,”

he added. “Hopefully, this project will lead us to a low-cost tool

that we can use to make sure everyone is working to prevent the

release of organisms into the environment, from universities to

manufacturing plants to DIY bio enthusiasts in their garages.”

Scientists create engineered microorganisms by introducing

new genes into their genomes that enable them to produce

valuable drugs, biofuels, or food products. A bacterium

containing the human gene for producing insulin, or a yeast

bearing multiple genes from several organisms to make the

antimalarial drug artemisinin are examples.

WE ARE EXCITED ABOUT THE PROMISE OF SYNTHETIC

BIOLOGY, BUT WE ALSO HAVE AN ETHICAL RESPONSIBILITY TO THINK ABOUT THE POTENTIALLY NEGATIVE USES OF THE TECHNOLOGIES WE DEVELOP.”

WPI chemical engineering professor Eric Young helps to develop new biosecurity tool

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BIOSECURITY TOOL TO DETECT ENGINEERED ORGANISMS IN WILD (CONT.)

‘NON-ENGINEERED COUSINS’

Because many of the genes in these engineered organisms

exist in nature, telling them apart from non-engineered

organisms in soil or water samples can be challenging. “It’s akin

to finding the proverbial needle in a haystack,” Young said.

He added that the key to making that distinction will be

identifying genetic signatures for each organism. By virtue

of the way they are produced, the majority of genetically

engineered organisms have one or more short sections of DNA

that are unique to their genomes and make them different

from their non-engineered cousins. These DNA signatures can

be used as markers to quickly spot an engineered organism

in a population of naturally occurring microorganisms.

Young’s role in the research project is to generate examples of

bioengineered organisms that contain these specific markers.

“We are supplying the ‘expert’ information the detection

device will look for,” he said. “We are taking into account the

genetic engineering of the past 50 years and reducing all of

that knowledge and information down to a set of essential

signatures for bioengineered organisms that we would most

likely need to find. It’s up to our sponsor and the team to

decide which organisms are important, and we help decide

what signatures we have to look at. It’s very exciting work.”

Initially, Young, who is working with two graduate students,

will focus on brewer’s yeast, which he says is increasingly

becoming the organism-of-choice for bioengineering

companies because it is easy to engineer and simple to grow,

given the decades of large-scale fermentation experience in

the brewing industry.

The signatures he is identifying will be useful for detecting

known engineered organisms that may have come from

corporate and university labs. Detecting potentially harmful

organisms that may have been intentionally released into the

environment will be a greater challenge.

“It’s a whole lot more complicated when you don’t know

what organisms you might need to look for,” he said. “We

have to think about what is most likely to be out there

and what would somebody with limited resources create.

We need to create tools that can detect a wide range of

engineered organisms. And they need to be flexible enough

that they could detect a specific set of signatures but then

detect newly added signatures as they are found. We are

helping develop a technology to do that.”

The knowledge Young is generating will ultimately be

incorporated into a benchtop detection device that will be

developed by other members of the research team. Other

team members are creating machine learning algorithms that

will find new signatures that experts may not identify.

Young said he expects a usable detection device for yeast

will be ready at the conclusion of the programme, but

it could be five to ten years before the more complex

challenges are solved.

WE HAVE TO THINK ABOUT WHAT IS MOST LIKELY TO BE OUT THERE

AND WHAT WOULD SOMEBODY WITH LIMITED RESOURCES CREATE.”

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DIGITAL MAGAZINE

2019 EDITORIAL SCHEDULE

#11 AUTUMN / FALL 2018 / WWW.BIOBASEDWORLDNEWS.COM

THE FIRST ‘COTTON + CORN’ SHOE FROM REEBOK’S SUSTAINABLE RANGE HITS THE SHOPS. “MOST ATHLETIC FOOTWEAR IS MADE USING PETROLEUM TO CREATE SYNTHETIC RUBBER AND FOAM CUSHIONING SYSTEMS. WITH 20 BILLION PAIRS OF SHOES MADE EVERY YEAR, THIS IS NOT A SUSTAINABLE WAY OF MAKING FOOTWEAR”

PROJECT FOCUS: HOW A BIO-BASED SOLUTION CAN SOLVE OUR PLASTIC TRAY PROBLEM.

CHANGE AND CONTINUITY - THE INSIDE STORY OF 10 YEARS OF THE NORDIC WOOD BIOREFINERY CONFERENCE (NWBC).

BAD NEWS FOR BIO-BASED CHEMICALS AS EU DECLARES THAT GENE EDITING IS GENETIC MODIFICATION.

HOW AN OUTDOOR CLOTHING BRAND AND THE BASQUE CIDER TRADITION HAVE PARTNERED TO CREATE NATURAL DYES.

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BRANDS: A PRAGMATIC APPROACH TO BIO-BASED CHEMICALS.

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PERFORMANCE IS KEY AS CHECKERSPOT PREPARES TO LAUNCH A PRODUCT FOR THE WINTER SPORTS MARKET

INSIDE THE ALLIANCE BETWEEN REG, EXXONMOBIL AND CLARIANT THAT IS REVOLUTIONISING CELLULOSIC BIOFUELS

THE PORT OF AMSTERDAM AS A CIRCULAR HOTSPOT: HOW A PORT SPEEDS UP THE CIRCULAR ECONOMY

HOW ALLBIRDS ARE PUTTING THEIR BEST FOOT FORWARD FOR BIO-BASED FOOTWEAR

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