Feb 18, 2021

Metagenomics: The superpower behind Zymergen’s biological database

The secret to designing breakthrough products is right beneath our feet 

soil can contain hundreds of millions of microbial genomes
A teaspoon of soil can contain hundreds of millions of microbial genomes, representing galaxies of hidden biological functions with the potential to make things like clothes, food, electronics, and even vaccines — all with previously impossible features.

Zymergen partners with nature to make better products in a better way. We do this using our powerful biofacturing platform, which lets us design, develop, and commercialize bio-based breakthrough products. An important part of that platform is our enormous database of biological building blocks, which puts nature’s molecular catalog at our fingertips. Our database lets us design bio-inspired products with incredible new properties that can’t be achieved with conventional chemistry.

And what makes our database so special? The answer is metagenomics.

Meta-ge-what?

Metagenomics is the study of genetic material recovered from environmental samples — like the soil in your backyard, pond water, or even the human gut microbiome. Whereas “genomics” is the study of the entire genome of a single organism, metagenomics is the study of all the genomes in an environment. And in many environments, that means a LOT of genomes. One gram of soil can contain more microbes than there are stars in the Milky Way galaxy.

What makes metagenomics even more fascinating is that the vast majority of these microbes have never been studied. Traditional microbiology depends on scientists’ ability to grow a microbe in the lab. It is estimated that < 1% of microbes in soil are easily cultured, meaning we have been missing out on >99% of microbial diversity. Metagenomics provides us with a way to study this unexplored microbial diversity. Every time we search our metagenomic database, we are likely the first humans to set eyes on that genomic information.

What makes metagenomics at Zymergen so important?

At Zymergen, we have amplified the power of metagenomics. We built a technology that gives us the highest resolution metagenomic data ever achieved. Most metagenomic studies of the soil give you tiny snippets of information. You can get glimpses of genes, but without any sense of how they all go together. Our technology lets us see long stretches of genomic information. Instead of single genes, we look at entire pathways.

Oliver Liu, Senior Director of Metagenomics

Why does this make a difference?

“Imagine you put a cookbook through a paper shredder,” explains Oliver Liu, Senior Director of Metagenomics in Zymergen’s Exploration & Discovery department. “You could find scraps of paper that say ‘eggs’ or ‘8 minutes’ or ‘tablespoon.’ You know what the words mean, but you can’t do very much with that information. Now imagine if you could reassemble an entire page. You would know not just the ingredients, but how they go together to make a cake. This is fundamentally what our databases enable.”

Nature has spent billions of years developing, modifying, and optimizing biological recipes for an almost infinite number of functions and applications. With our metagenomics platform, we read these recipes, marvel at the diversity that exists in nature, and use them as guidance and inspiration for our own inventions.

This sounds exciting — so how can we use this?

Metagenomics plays an important role in the development of products like Hyaline, our bioelectronic film. We have created powerful, purpose-built systems that draw from the information in our metagenomic database to find interesting natural molecules (ZYNC) and design metabolic pathways to make them (Automated Pathway Explorer). These give us the individual genes that go into these pathways, and also teach us how these genes can fit together to give us what we want.

Here are a few more specific ways that metagenomics helps speed never-before-imagined products to market:

  • We can identify novel metagenomic enzymes that can catalyze reactions faster, more efficiently, and/or with different specificity than anything found in public databases. These enzymes often look very different from what has previously been known.
  • The biosynthetic pathways for many interesting natural molecules have never been discovered. We can use metagenomics to uncover these cryptic pathways.
  • We adapt useful proteins that nature has evolved to detect certain small molecules or regulate their production to optimize the biological systems we create.
  • We can identify millions of biosynthetic gene clusters that encode completely novel biological small molecules (at least novel to humans) that we are exploring for interesting properties and activities.
  • The metagenome can be thought of as a massive dataset. Our data scientists comb through these data with machine learning approaches that can then be used to improve our own biological designs.

What’s wrong with how we make things now?

Most everything around us is made with petrochemistry, from clothes to cosmetics to fertilizers. A century of petrochemistry has brought some amazing breakthroughs, but we’re reaching the limits of what can be made with these hydrocarbons. Making materials and products out of the same small set of petrochemicals is not only limiting, it’s unsustainable, requiring high-energy reactions and releasing climate changing gases into the environment.

We’re just scratching the surface of what biology can do, but we believe biofacturing creates better products faster, cheaper, and more sustainably than traditional chemistry.

The meta-future

Looking ahead, our metagenomics database can hyper-accelerate the process of creating valuable biological molecules with the potential to make things like clothes, food, electronics, and even vaccines — all with previously impossible features.

Combined with our automation and machine learning capabilities, Zymergen’s metagenomic database is a critical part of our biofacturing platform. It’s an important tool for designing the bio-inspired products of tomorrow with incredible new properties we can only imagine today.