In an exclusive conversation ahead of his panel appearance at SynBioBeta 2025 next week in San Jose, Kareem Barghouti, CEO of Pragma Bio, sat down with us to delve into a pioneering approach that's turning gut microbes into potential blockbuster drugs.

Synthetic biology, he argues, isn’t just an emerging tool—it’s a paradigm shift, fundamentally altering how researchers approach drug discovery. Barghouti's company, Pragma Bio, is at the forefront of this revolution, tapping into a previously overlooked resource: the human gut microbiome.

"Our gut microbes are producing small molecules with powerful therapeutic potential—many of which we've only just begun to identify," Barghouti emphasizes. His excitement is palpable when he describes the microbiome as more than just bacteria residing within us; it's "a treasure trove of therapeutics."

Pragma Bio distinguishes itself by moving beyond traditional microbiome research methods, which have typically catalogued bacteria species. Instead, they're mining the genetic blueprints hidden within microbial metagenomes—the total genomic content of these ecosystems—to identify novel bioactive compounds. "We're uncovering how microbes produce natural compounds that act like nature’s own medicine cabinet," Barghouti explains.

This is precision medicine reinvented. By leveraging synthetic biology, Pragma Bio synthesizes these microbial gene clusters in controlled laboratory environments, systematically assessing each molecule’s immune-modulating capabilities. It's an approach Barghouti calls "genome-informed biosynthesis," a technique he firmly believes will define the future of drug discovery.

But innovation isn't without challenges. One critical barrier Pragma Bio tackles head-on is the complexity of expression hosts—microbes engineered to produce therapeutic compounds reliably. “Not all microbes—or chassis organisms—are equally suited for expressing complex microbial pathways,” Barghouti points out. He stresses that selecting the right host, optimizing pathways, and ensuring expression fidelity are crucial steps for scaling synthetic biology from intriguing concept to actionable therapy.

For Barghouti, the intersection of synthetic biology and microbiome science is intensely personal and intellectually motivating. "Natural products have long been a rich source of pharmaceuticals—but for decades, drug discovery stalled because the ‘low-hanging fruit’ had already been picked," he reflects. “Synthetic biology is giving us a ladder to reach the rest of the tree.”

And that "tree" grows remarkably close to home. Unlike traditional bioprospecting efforts in soil or marine environments, Pragma Bio focuses exclusively on the human gut. According to Barghouti, this strategic pivot toward internally co-evolved microbial metabolites could unlock more targeted, efficacious, and safer immune therapies.

Despite the breakthroughs, Barghouti remains pragmatic about the pace of innovation. "Unlocking these molecules takes patience," he admits, yet quickly adds an optimistic note: "But the tools now exist—and with sustained investment, synthetic biology can become a consistent engine for therapeutic discovery."

Barghouti’s vision positions synthetic biology not merely as a manufacturing technology but as a powerful drug discovery engine—a core enabler of next-generation precision medicine. He believes this moment signals a critical inflection point for the field.

"We’re not just studying microbes—we’re discovering new medicines," Barghouti says confidently. "Synthetic biology has always been about unlocking what nature does best—only faster, more precisely, and more reliably."

As Barghouti prepares to take the stage at SynBioBeta, one thing is clear: Pragma Bio isn’t merely riding the wave of synthetic biology innovation—they’re creating it.

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‍Sources: Direct interview with Kareem Barghouti (April 2025), provided via SynBioBeta communication.

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