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Synthetic Biology vs Synthetic Chemistry: A Primer

At Antheia, we spend a lot of time talking about synthetic biology due to the nature of our work engineering yeast to produce active pharmaceutical ingredients (APIs) and key starting materials (KSMs) for essential medicines. However, synbio’s cousin, the long established field of synthetic chemistry, still plays a vital role. This blog is an introduction and primer for a series about synthetic chemistry, where we’ll discuss the ways that synthetic chemistry complements synthetic biology and biopharma manufacturing.

We invite you to follow along as we explore how synthetic chemistry supports us in unleashing the power of nature to discover new medicines and generate a more efficient, resilient, and equitable pharmaceutical manufacturing model.

Synthetic Chemistry, Defined

Broadly speaking, synthetic chemistry is about transforming matter from one compound into another, and it is especially about creating compounds with new properties. Usually when people think of synthetic chemistry or chemical synthesis, glassware, organic solvents, and metal catalysts come to mind. In contrast, synthetic biology and biotechnology evoke images of cells and enzymes, where living cultures are making a product. But here at Antheia we’re very familiar with the fact that these definitions aren’t absolute and, importantly, that we can combine these two technologies.

We would define traditional synthetic chemistry as the physical or chemical manipulation of substances in a controlled lab environment to produce specific chemical reactions that yield desired formulations. Synthetic chemistry often entails a multi-step process that requires successive rounds of purification and processing to produce a final chemical product – this is often referred to as long chemical synthesis. Synthetic biology may also be used to perform long chemical syntheses, as we do in our work at Antheia, though with some differences from what we would call traditional synthetic chemistry. One differentiating feature between chemical synthesis and biosynthesis is that biosynthesis always utilizes biological components in either living or synthetic cells. Synthetic biology also takes advantage of biological components, but can extend beyond the limitations of biosynthesis in natural systems.

In biotechnology, for example, in vitro biocatalysis is the practice of using biologically produced materials, such as enzymes, that have been extracted or purified first, to perform chemical reactions. Which category would such a process fall within? We would argue that it is most appropriately categorized as synthetic chemistry, in that you are adding enzymes to a chemical reaction like you would any other component. The development of engineered enzymes to perform these reactions would constitute synthetic biology, though these reactions would still not be considered biosynthesis because it is done outside of a living cell. Leveraging enzymes for in vitro biocatalysis can offer important advantages over traditional synthetic chemistry pathways, such as catalyzing reactions more quickly, enabling reactions with selectivities that may be otherwise impossible with non-enzyme catalysts, and performing these reactions in environmentally sustainable conditions. But it still has one major disadvantage: you must obtain the enzymes to run the reaction yourself. For manufacturing at scale, large amounts of purified protein that retains its activity is required. This is an expensive, lengthy, and laborious task fraught with potential errors such as protein misfolding and low yields.

There is a saying that the best chemical reaction is the one that you don’t have to do – and unfortunately, synthetic chemistry is defined entirely by reactions that you do. In contrast, biosynthesis puts the cells to work. Using the genes we insert into the cell as templates, the cell produces all of the necessary enzymes, cofactors, and substrates needed, largely from simple sugars, and then performs all of the reactions necessary to produce our product of interest. At Antheia, we draw a fine line here between how we talk about synthetic chemistry and synthetic biology; while these reactions might be making the same products from the same inputs, even at times using the same enzymes to get it done, in synthetic chemistry, scientists must do the work, and in biosynthesis the cells do the work.

Complementary Tools

That fine line is a great thing to highlight for the purposes of this primer. However, highlighting that separation between the two processes – synthetic biology and synthetic chemistry – is less critical in practice. In our biomanufacturing, they are complementary tools that work together harmoniously, so we have little need to categorize them so starkly in our work. Antheia relies on them both, using each tool in order to maximize the potential of the other.

In synthetic biology, some of the plant natural product pathways are dozens of steps long. That means dozens of usually very chemically similar intermediates, often happening all in the same cell simultaneously, as you would see in a plant in nature. Within a cell, you’ll find a soup of similar-looking molecules – each enzyme is able to find and interact with its preferred substrate, and perform a specific reaction, all under the same conditions.

Similarly, when synthetic chemistry is combined with synthetic biology, we find that enzymes can accomplish a lot of things that traditional small molecule catalysts cannot:

This all equates to a level of efficiency that traditional synthetic chemistry lacks, since without the dance of enzyme-substrate selectivity, teams must cope with individual isolation and purification of lots of intermediates, and also the need to set up each subsequent step, often under very different conditions than the previous step.

This is why many chemists will tell you that the worst part of any synthesis is purification. It is a necessary step because chemical reactions, unlike enzymatic reactions with their substrate selectivity, tend to be relatively non-discriminatory. That means with each round of chemical synthesis, you may end up with increasing numbers of intermediate outputs to separate and purify. Synthetic biology offers huge potential to replace not just one individual step of chemical synthesis with a biosynthetic step – but to replace multiple consecutive steps that would otherwise require laborious purifications and different reaction conditions for each step. With synthetic biology, a cell can do all these steps under the same conditions with no purifications necessary. It is simply one of many appealing examples of where synthetic biology can complement synthetic chemistry, and create transformative efficiency.

Conclusion

Synthetic chemistry and synthetic biology are powerful tools that can complement each other to allow new and easy access to a wider range of molecules than we have ever been able to produce before. While we seek to use synthetic biology to reduce much of the work of synthetic chemistry – by engineering biosynthetic pathways to produce molecules that we previously relied on nature and synthetic chemistry to produce – we don’t view synthetic biology as being in conflict with synthetic chemistry. Instead, synthetic chemistry informs every part of our work at Antheia – we rely on synthetic chemistry to probe and understand the reactions occurring in our yeast cells so that we can engineer the enzymes and strains to work better for us.

In the next installment of Antheia’s Synthetic Chemistry Series, we’ll dive deeper into how synthetic chemistry supports innovation, and begin to evaluate the challenges of synthetic chemistry, and its applications in the pharmaceutical space.

Richard Sherwin

Head of Commercialization

Richard is an industry veteran with more than 30 years of experience in the KSM, API, and intermediate markets. He is responsible for leading the commercialization and revenue generation for Antheia’s robust pipeline of products. Richard brings an exceptional track record of leading international sales teams, driving revenue growth, building strategic partnerships, and delivering innovative products to market, including ANDA and NDA developments. Richard led commercial efforts at some of the leading global pharmaceutical companies and most recently, built his own consultancy business advising a range of clients, including $1B divisions of major multinationals.

Appropriate regulatory submissions will be prepared and submitted to support Antheia’s customers who need to reference and access necessary process-related information.

Yihui Zhu, PhD

Head of Fermentation

Yihui leads the fermentation team at Antheia. With over 25 years of hands-on experience in the field, he brings in-depth knowledge and expertise in microbial metabolism and fermentation process development. He is also skilled in developing comprehensive fermentation data collection, analysis, and visualization systems. Prior to joining Antheia, he served as a fermentation lead at Intrexon and Codexis where he successfully built fermentation labs and teams and led multiple biofuel and biochemical projects to reach stretch milestones and tech transfer. Yihui is passionate about the potential of fermentation and is dedicated to advancing the field through innovative research and development.

Yen-Hsiang Wang, PhD

Head of Strategy, Partnerships, and Finance

Yen-Hsiang leads strategy, partnerships and finance at Antheia. He completed his M.S. and Ph.D. in Bioengineering at Stanford, with extensive research experience in synthetic biology, metabolic engineering and computational modeling. Before joining Antheia, he worked at McKinsey and Tencent with a strong focus in corporate strategy and big data/advanced analytics. At Tencent, he served as Director of Strategy and Business Development for the AI Lab, leading corporate initiatives in healthcare AI/ML applications and commercialization. He also served in AI4H (Artificial Intelligence for Health), a collaboration between WHO and ITU, to establish global standards for AI in healthcare.

Audrey Wang

Head of Financial Planning and Analysis

Audrey leads financial planning and analysis at Antheia. With an MBA from Washington University in St. Louis, Audrey is passionate about leveraging financial analysis, digital technology, and data analytics to guide companies in making optimal investments and strategic business decisions. Audrey has a decade of experience in helping companies solve unique problems and creating long-term impact with unconventional approaches. Before joining Antheia, she was at Vir Biotechnology and Merck where she led various FP&A workstreams, including investment valuation, asset prioritization, and manufacturing sites operation finance support. Audrey completed CFA Level II and passed the U.S. CPA exam in 2011.

Antonij Tjahjadi, CPA

Head of Accounting

Antonij Tjahjadi leads accounting at Antheia and holds active CPA license. He joined Antheia with more than 20 years of experience in corporate accounting, bringing deep expertise in ramping up accounting operations for start-up companies, SEC reporting/technical accounting, and SOX implementation efforts. Before joining Antheia, he held various leading roles in both public and private company settings, including directing accounting functions at Ambys Medicines, where he successfully implemented Netsuite with Point Purchasing integration and set up various accounting policies and processes, and played a key role in the initial public offering of Nutanix, Inc.

Ken Takeoka

Head of Biology

Ken leads the Biology team at Antheia, which incorporates both strain and protein engineering functions. He has more than 16 years of experience in the synthetic biology field, working with leading companies, including Amyris and Novartis. One of his passions is molecular biology tool development and he previously worked to build the foundation for the automated strain engineering pipeline at Amyris. At Novartis, he modernized the molecular biology techniques and established a platform to model mechanisms of antibiotic resistance in a range of organisms.

Suzanne Sato

Head of Downstream Processing

Suzy leads downstream chemistry processes at Antheia. She has 19 years of experience in process development, including route development through synthetic chemistry and scale-up of small molecule APIs for GPCR targets under cGMP for Phase I-III trials. Before joining Antheia, Suzy led a full DSP team at Amyris where she successfully pivoted developments from biofuels hydrocarbon products to pharmaceutical intermediate, flavor, fragrance and nutraceutical products. She led a team that scaled 11 products and took five products to commercial manufacturing.

Farrah Pulce, PMP

Head of Project Management

Farrah leads program and project management at Antheia. She has over 20 years of experience leading program and project management, operations, and engineering for companies across the CPG, aerospace, and automotive industries. Prior to joining Antheia, Farrah implemented and led the sustaining program management team at Impossible Foods. She also led product operations, project management, and cost optimization at Blue Bottle Coffee and Tyson Foods to develop and commercialize new products. As a certified project management professional (PMP), Farrah has a proven record of successful project delivery, improving project management practices, and building collaborative teams.

Jordyn Lee

Head of Communications

Jordyn leads communications and external affairs at Antheia. She brings a decade of multidisciplinary communications experience in helping companies make complex science and technology accessible to broad audiences, all while maintaining technical accuracy and integrity. She has a passion for visionary storytelling and translating impact across the entire communications ecosystem – her work has spanned from public relations to corporate communications to marketing. Jordyn has served as an advisor to a number of different life sciences companies and most recently led corporate communications at Amyris.

Ben Kotopka, PhD

Head of Data Science

As Head of Data Science at Antheia, Ben manages in-house software development and external partnerships for storing and interpreting research data, executing bioinformatics analyses, and streamlining business processes. Prior to Antheia, Ben worked as an academic researcher at the intersection of machine learning, bioinformatics, and synthetic biology. Following this, as an entrepreneur and consultant, he developed and deployed data science solutions for biotechnology applications ranging from metabolomics-driven compound discovery to MRI segmentation.

Guerin Kob

Head of Supply Chain

Guerin is responsible for leading the design, development, management and improvement of Antheia’s end-to-end global supply chain. He has over 15 years of experience leading high-performing supply chain and procurement teams at leading biotechnology and specialty chemical companies, with extensive experience in process development and end-to-end supply chain optimization. Prior to joining Antheia, Guerin served as Senior Director of Global Supply Chain for Sumitomo Chemical’s biotechnology division with Valent Biosciences, where he led the end-to end supply chain including procurement, logistics and distribution, integrated business planning, materials management, customer service, and supply planning functions globally.

Pavel Aronov, PhD

Head of Bioanalytics

Pavel leads the Bioanalytics team at Antheia. He has 20 years of experience in analytical and clinical chemistry, mass spectrometry, chromatography, and metabolomics. Pavel built and led the original Chemistry and Analytics team at Impossible Foods enabling strain development, fermentation, DSP, regulatory, QC, and scale-up of leghemoglobin biomanufacturing. During his academic career at UC Davis and Stanford University Pavel developed a vitamin D assay used by all major clinical diagnostics laboratories and pioneered metabolomics studies to investigate kidney disease and microbiome.

Jesse Ahrendt

Head of Quality Assurance and Regulatory Affairs

Jesse has more than 25 years of experience in regulatory affairs, quality systems, manufacturing quality, and regulated industries, ranging from early- to late-stage pharmaceuticals, biomanufacturing, consumer care, and medical devices. He has supported global product launches and the underlying quality supply chain components in industries that require strict adherence to internationally accepted quality standards. Before Antheia, he led quality efforts at Zymergen and Sandoz, and supported many global pharmaceutical companies during his time in Biotech Consulting at NSF International, all to bring quality to the forefront in manufacturing, standardize global processes, and support customer regulatory requirements.

Heidi Pucel

Chief People Officer

Heidi is a results-driven human resources executive and HR business partner who leverages decades of experience in empowering, motivating, and inspiring to drive transformation within high-performing and rapidly-growing workforces. A certified executive coach and passionate advocate for people-oriented solutions, Pucel serves as a partner to executive teams to design programs that support employee development, engagement, and recruitment and retention. Pucel most recently served as Chief People Officer for Countsy, where she worked as an interim HR executive for clients in the biotechnology and software industries, such as Ceribell and Tune Therapeutics.

Zack McGahey

Chief Operating Officer

Zack is a leading executive in operations management, specializing in bioprocess engineering and manufacturing management. He has over 20 years of experience leading manufacturing functions for companies across the pharmaceutical, synthetic biology, diagnostics, and automotive industries. Before joining Antheia, Zack was VP of manufacturing and capex project management at Zymergen. He also gained experience managing commercial scale facilities operations for Tesla, where he was responsible for managing 10 million square feet of factory, lab and warehouse space during the Model 3 ramp.

Kristy Hawkins, PhD

Co-Founder & CSO

Kristy has over 20 years of experience in the field of synthetic biology, focusing on yeast metabolic engineering for the production of small molecules. She did the founding work on the benzylisoquinoline alkaloid pathway during her graduate studies and gained valuable industry experience at Amyris and Lygos. Kristy is an expert in tool development, high-throughput screening, and host strain and heterologous pathway engineering.

Christina Smolke, PhD

Co-Founder & CEO

Christina is a pioneer in synthetic biology and metabolic engineering, where she has over 20 years of experience. As Professor of Bioengineering and Chemical Engineering at Stanford University, her laboratory led the breakthrough research to engineer baker’s yeast to produce some of the most complex and valuable medicines known. Under her leadership, Antheia’s synthetic biology platform enables new possibilities for drug discovery and efficient, sustainable, transparent, and on-demand drug manufacturing at scale. Her vision and accomplishments have garnered numerous awards, including the Chan-Zuckerberg Biohub Investigator, NIH Director’s Pioneer Award, Nature’s 10, Novozymes Award for Excellence in Biochemical Engineering, and TR35 Award.

U.S. Secretary of State Antony J. Blinken visits Antheia to discuss biotechnology innovation

Appropriate regulatory submissions will be prepared and submitted to support Antheia’s customers who need to reference and access necessary process-related information.