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The Natural Synergy Between Synthetic Chemistry and Synthetic Biology

At Antheia, we spend a lot of time talking about synthetic biology due to the nature of our work engineering yeast to produce key starting materials (KSMs) and active pharmaceutical ingredients (APIs) for essential medicines. However, synbio’s cousin, the long-established field of synthetic chemistry, plays a vital role. This is the third and final blog in an educational series about synthetic chemistry. If you missed them, you can find part one here, and part two here.  As we’ve discussed in this series, synthetic chemistry has long been the backbone of small-molecule drug development. However, certain molecules – either due to their size, configuration, or characteristics – remain difficult or even impossible to synthesize by current synthetic chemistry processes.  Drug development and manufacturing is an expensive and arduous process. Limitations of synthetic chemistry can add significantly to the cost and time needed to produce challenging targets, leaving potentially valuable medicines out of reach with current techniques. This means that while current synthetic chemistry approaches to drug development are responsible for the efficient and scalable production of thousands of therapeutics, this process remains limited by what it can achieve alone. The solution to synthetic chemistry’s shortcomings may lie in biosynthesis – the synthesis that occurs naturally in living cells. Is biosynthesis a magic bullet? The goal of drug development is to identify specific compounds with targeted effects. In an ideal scenario, a good drug candidate recognizes its target molecule by binding to it and having a  desired effect, such as an agonistic or antagonistic effect on a receptor for example.  Determining drug candidates with that level of specificity is no simple task, but when it comes to problem-solving, the natural world is full of solutions. Due to the limitations inherent with synthetic chemistry, only a small portion of the chemical space is accessible for drug development and discovery, therefore limiting pharmaceutical innovation. With biosynthesis, we are able to unlock much more of chemical space and access vast, underexplored opportunities for drug development and discovery.   Biology has mastered the art of synthesizing big, complex, and specific molecules. In direct contrast to synthetic chemistry, biosynthesis occurs in the aqueous environment of the cell, opening up a new range of molecules historically underrepresented by synthetic chemistry. Additionally, these living systems have undergone millennia of evolution to produce enzymes that can precisely recognize, bind, and configure molecules with a specificity that synthetic chemists can only dream of. But biology has its own limitations. Evolution is famously a tinkerer and not an engineer. Natural solutions that have evolved are adapted specifically to solve the inherent problems they face. To meet the challenges in modern drug development and ultimately make a meaningful impact on patients, we need to engineer enzymes to perform new reactions, in new environments, and at improved levels of activity. We can achieve just that by combining the best of synthetic chemistry and synthetic biology.  The best of both worlds Synthetic biology allows us to re-engineer enzymes to fit our needs. Synbio also unlocks whole organisms as potential production platforms; by engineering pathways for each step of chemical synthesis, we can turn microbes into factories to produce our target molecules using fermentation.  Synthetic chemistry, despite its constraints in producing certain types of compounds, will continue to play a major role by adding to the diversity of structures we can access and analyze. Where nature solved problems by evolving chemical solutions, their structures are blueprints that synthetic chemistry processes can complement and enhance.   Together, the potential synergy between synthetic chemistry and synthetic biology is enormous. Enzymes engineered specifically to function in synthetic chemistry environments can act as in vitro biocatalysts, adding specificity to synthetic chemistry reactions and potentially reducing costly purification steps. Similarly, synthetic chemistry’s understanding of structure informs which amino acids impact key characteristics of our engineered enzymes, such as rigidity, solubility, and coordination with the substrate. Antibiotics best illustrate the combination of biology and synthetic chemistry coming together. The penicillins used today are not natural products but are the result of chemists tinkering with the original compounds accidentally discovered by Alexander Fleming. The commonly prescribed antibiotic amoxicillin is a prime example – Penicillin G is produced by Penicillium chrysogenum and chemically converted to amoxicillin. These semi-synthetic derivatives allow us to develop new antibiotics effective against pathogenic bacteria that have long ago evolved resistance to their natural counterparts. As antibiotic resistance continues to evolve, it may be necessary to utilize every tool in our biological and chemical arsenal to develop the next generation of antibiotics. Thus, combining synthetic biology and synthetic chemistry opens up new possibilities in biological synthesis and downstream augmentation. This creates a far bigger and more dynamic space for drug discovery, development, and manufacturing. Complementary technology At Antheia, our platform is primarily built around the power of synthetic biology and biosynthesis, and we also leverage other approaches, including chemical synthesis, to make complex molecules – key starting materials (KSMs) and active pharmaceutical ingredients (APIs) –  with proven medicinal value and well-established markets. These molecules often have long metabolic pathways and pose a challenge for both biological engineering and synthetic chemistry approaches. Our goal is to transfer these pathways, typically originating from plants, into yeast cells that can be efficiently used as a biomanufacturing platform at industrial scales. Transferring an entire metabolic pathway to another organism comes with several challenges. The major issue from the biosynthesis perspective is that the enzymes did not evolve to function in yeast cells and therefore may be less active in that environment, so we must re-engineer or rebuild certain enzymes to perform in their new host.  Evolution optimizes enzymes to perform their required functions in their natural environments. In the lab, we need these enzymes to work in new environments and often to perform new functions, whether that’s working faster, longer, or performing new reactions. We can use evolution as a tool to continue the job of optimizing and improving enzymes for their new roles. We iterate on these improved enzymes until they are capable of

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.