Expanding the biosynthetic pathway via retrobiosynthesis

January 13, 2021

KAIST metabolic engineers presented the bio-based production of multiple short-chain primary amines that have a wide range of applications in chemical industries for the first time. The research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering designed the novel biosynthetic pathways for short-chain primary amines by combining retrobiosynthesis and a precursor selection step.

The research team verified the newly designed pathways by confirming the in vivo production of 10 short-chain primary amines by supplying the precursors. Furthermore, the platform Escherichia coli strains were metabolically engineered to produce three proof-of-concept short-chain primary amines from glucose, demonstrating the possibility of the bio-based production of diverse short-chain primary amines from renewable resources. The research team said this study expands the strategy of systematically designing biosynthetic pathways for the production of a group of related chemicals as demonstrated by multiple short-chain primary amines as examples.

Currently, most of the industrial chemicals used in our daily lives are produced with petroleum-based products. However, there are several serious issues with the petroleum industry such as the depletion of fossil fuel reserves and environmental problems including global warming. To solve these problems, the sustainable production of industrial chemicals and materials is being explored with microorganisms as cell factories and renewable non-food biomass as raw materials for alternative to petroleum-based products. The engineering of these microorganisms has increasingly become more efficient and effective with the help of systems metabolic engineering - a practice of engineering the metabolism of a living organism toward the production of a desired metabolite. In this regard, the number of chemicals produced using biomass as a raw material has substantially increased.

Although the scope of chemicals that are producible using microorganisms continues to expand through advances in systems metabolic engineering, the biological production of short-chain primary amines has not yet been reported despite their industrial importance. Short-chain primary amines are the chemicals that have an alkyl or aryl group in the place of a hydrogen atom in ammonia with carbon chain lengths ranging from C1 to C7. Short-chain primary amines have a wide range of applications in chemical industries, for example, as a precursor for pharmaceuticals (e.g., antidiabetic and antihypertensive drugs), agrochemicals (e.g., herbicides, fungicides and insecticides), solvents, and vulcanization accelerators for rubber and plasticizers. The market size of short-chain primary amines was estimated to be more than 4 billion US dollars in 2014.

The main reason why the bio-based production of short-chain primary amines was not yet possible was due to their unknown biosynthetic pathways. Therefore, the team designed synthetic biosynthetic pathways for short-chain primary amines by combining retrobiosynthesis and a precursor selection step. The retrobiosynthesis allowed the systematic design of a biosynthetic pathway for short-chain primary amines by using a set of biochemical reaction rules that describe chemical transformation patterns between a substrate and product molecules at an atomic level.

These multiple precursors predicted for the possible biosynthesis of each short-chain primary amine were sequentially narrowed down by using the precursor selection step for efficient metabolic engineering experiments.

"Our research demonstrates the possibility of the renewable production of short-chain primary amines for the first time. We are planning to increase production efficiencies of short-chain primary amines. We believe that our study will play an important role in the development of sustainable and eco-friendly bio-based industries and the reorganization of the chemical industry, which is mandatory for solving the environmental problems threating the survival of mankind," said Professor Lee.
-end-
This paper titled "Microbial production of multiple short-chain primary amines via retrobiosynthesis" was published in Nature Communications. This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science and ICT through the National Research Foundation (NRF) of Korea.

-About KAIST

KAIST is the first and top science and technology university in Korea. KAIST was established in 1971 by the Korean government to educate scientists and engineers committed to the industrialization and economic growth of Korea.

Since then, KAIST and its 64,739 graduates have been the gateway to advanced science and technology, innovation, and entrepreneurship. KAIST has emerged as one of the most innovative universities with more than 10,000 students enrolled in five colleges and seven schools including 1,039 international students from 90 countries.

On the precipice of its semi-centennial anniversary in 2021, KAIST continues to strive to make the world better through the pursuit in education, research, entrepreneurship, and globalization.

The Korea Advanced Institute of Science and Technology (KAIST)

Related Engineering Articles from Brightsurf:

Re-engineering antibodies for COVID-19
Catholic University of America researcher uses 'in silico' analysis to fast-track passive immunity

Next frontier in bacterial engineering
A new technique overcomes a serious hurdle in the field of bacterial design and engineering.

COVID-19 and the role of tissue engineering
Tissue engineering has a unique set of tools and technologies for developing preventive strategies, diagnostics, and treatments that can play an important role during the ongoing COVID-19 pandemic.

Engineering the meniscus
Damage to the meniscus is common, but there remains an unmet need for improved restorative therapies that can overcome poor healing in the avascular regions.

Artificially engineering the intestine
Short bowel syndrome is a debilitating condition with few treatment options, and these treatments have limited efficacy.

Reverse engineering the fireworks of life
An interdisciplinary team of Princeton researchers has successfully reverse engineered the components and sequence of events that lead to microtubule branching.

New method for engineering metabolic pathways
Two approaches provide a faster way to create enzymes and analyze their reactions, leading to the design of more complex molecules.

Engineering for high-speed devices
A research team from the University of Delaware has developed cutting-edge technology for photonics devices that could enable faster communications between phones and computers.

Breakthrough in blood vessel engineering
Growing functional blood vessel networks is no easy task. Previously, other groups have made networks that span millimeters in size.

Next-gen batteries possible with new engineering approach
Dramatically longer-lasting, faster-charging and safer lithium metal batteries may be possible, according to Penn State research, recently published in Nature Energy.

Read More: Engineering News and Engineering Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.