The Rare 22nd Amino Acid for Methane – Producing Microbes

Pyrrolysine, often called the “22nd amino acid,” is a unique building block used by certain microbes to produce methane, a key energy source for them. Unlike common amino acids, it’s found only in specific archaea and bacteria, playing a specialized role in their metabolism. In this article, we’ll explore what pyrrolysine is, its biological function, and its relevance to health, all in a friendly, easy-to-read way for health-conscious readers.

Chemical Identity and Type

Pyrrolysine is an amino acid, specifically a non-standard, proteinogenic amino acid with the chemical formula C12H21N3O3. It’s a modified form of lysine, featuring a 4-methylpyrroline-5-carboxylate group linked to the ε-amino group of lysine via an amide bond. This structure gives it a positively charged pyrroline ring, similar to lysine, but tailored for specific enzymatic roles. Pyrrolysine is encoded by the UAG codon (normally a stop signal) in certain microbes, making it a rare addition to the genetic code alongside selenocysteine. Think of it as a specialized tool used by methane-producing microbes to perform unique biochemical tasks.

Biological Role and Benefits

Pyrrolysine is critical in specific microbes but has no direct role in human biology. Its key functions include:

• Methane Production: In methanogenic archaea (like Methanosarcina barkeri) and some bacteria, pyrrolysine is essential for enzymes (methylamine methyltransferases: MtmB, MtbB, MttB) that initiate methane production from methylamines (mono-, di-, and trimethylamine). It activates and orients methylamines for methyl group transfer, a vital step in these microbes’ energy metabolism.
• Enzyme Functionality: The pyrroline ring in pyrrolysine binds methylamines at its imine bond, positioning them for efficient chemical reactions with corrinoid proteins, driving methane synthesis.
• Genetic Code Expansion: Pyrrolysine’s unique encoding (via the UAG codon) makes it a model for studying how organisms expand their genetic code, potentially inspiring synthetic biology innovations.

While pyrrolysine doesn’t directly benefit human health, understanding its role in microbes can inform research into microbial ecosystems, gut health, or biotechnological applications like protein engineering.

Dietary or Natural Sources

Pyrrolysine is not found in human diets or produced by the human body. It’s synthesized by specific archaea and bacteria (e.g., Methanosarcina species, Desulfitobacterium hafniense) from two lysine molecules through a complex pathway involving the pylBCD genes:

• Biosynthesis: The enzyme PylB converts lysine to (3R)-3-methyl-D-ornithine, which PylC ligates to another lysine. PylD then oxidizes this intermediate, forming pyrrolysine after cyclization and dehydration.
• No Dietary Sources: Since humans don’t produce or use pyrrolysine, it’s not present in foods or supplements. However, supporting gut microbial health with a balanced diet (fiber-rich foods like vegetables, fruits, and whole grains) may indirectly support methane-producing microbes that use pyrrolysine.

Signs of Imbalance or Dysfunction

Pyrrolysine imbalances are irrelevant to human health since humans don’t produce or rely on it. However, disruptions in pyrrolysine synthesis in microbes could affect their methane production, potentially altering gut microbial ecosystems:

• Microbial Imbalance: In theory, reduced pyrrolysine in gut archaea could disrupt methane production, possibly affecting gut gas levels or microbial balance, though this is not well-studied in humans.
• No Human Symptoms: There are no known human symptoms tied to pyrrolysine, as it’s specific to certain microbes.

If you’re concerned about gut health or methane-related issues (e.g., bloating), consult a healthcare provider to assess microbial imbalances or digestive conditions.

Supporting Optimal Levels or Function

Since pyrrolysine is not used by humans, there’s no need to support its levels directly. However, you can promote a healthy gut microbiome, which may include pyrrolysine-using archaea, with these tips:

• Eat Fiber-Rich Foods: Vegetables, fruits, legumes, and whole grains (e.g., oats, beans, apples) feed beneficial gut microbes, potentially supporting methane-producing archaea.
• Stay Hydrated: Drink 8–10 cups of water daily to support digestion and microbial health.
• Include Fermented Foods: Yogurt, kefir, or sauerkraut can promote a diverse gut microbiome, indirectly supporting microbial ecosystems.
• Limit Processed Foods: Reduce high-sugar or high-fat processed foods to avoid disrupting gut microbial balance.
• Exercise Regularly: Moderate activity (30 minutes most days) like walking or yoga supports gut health and microbial diversity.

Safety, Interactions, and Precautions

Pyrrolysine has no direct role in human health, so there are no specific safety concerns or interactions for humans:

• No Supplements: Pyrrolysine is not available as a supplement, as it’s specific to certain microbes and not used by human cells.
• Gut Microbiome Context: Excessive methane production by pyrrolysine-using archaea in the gut could contribute to bloating or digestive discomfort in some people, but this is rare and requires medical evaluation.
• Biotechnological Use: Pyrrolysine’s PylRS/tRNA system is used in synthetic biology to incorporate non-standard amino acids into proteins. This is a research tool, not a health concern, but it highlights pyrrolysine’s broader scientific importance.

Fun Fact

Pyrrolysine, discovered in 2002 in Methanosarcina barkeri, is nicknamed the “22nd amino acid” because it’s one of only two amino acids (with selenocysteine) added to the standard 20 in the genetic code. Its ability to “hijack” a stop codon (UAG) for protein synthesis amazed scientists, revealing how nature creatively expands life’s building blocks!

Citations

1. National Institutes of Health. (n.d.). Pyrrolysine and Genetic Code Expansion.
2. Hao B, et al. (2004). Reactivity and chemical synthesis of L-pyrrolysine. Chem Biol.
3. Krzycki JA. (2011). The complete biosynthesis of pyrrolysine from lysine. Nature.
4. World Health Organization. (2022). Gut Microbiome and Health.
5. StatPearls – NCBI Bookshelf. (2023). Methanogenic Archaea and Pyrrolysine.