Pathway · 7 proteins
Biotin and lipoate
Biotin supports carboxylation; lipoate is attached to recipient proteins.
How it works
- Biotin is built from pimelate chemistry: dethiobiotin synthase closes the ring, and biotin synthase (BioB), a radical-S-adenosylmethionine enzyme, inserts the sulfur that makes biotin.
- Biotin is attached to its recipient carboxylases by biotin--[acetyl-CoA-carboxylase] ligase. The recipients include the acetyl-CoA carboxylase that commits acetyl-CoA to fatty-acid synthesis.
- Lipoate is made by a LipS1 family lipoyl synthase, also radical-SAM, and attached by lipoate--protein ligase to the E2 subunits of 2-oxoacid dehydrogenase complexes. Neither cofactor acts free: both function only when covalently bound to their target protein.
Grouped by the atlas’s curated pathway map. The table order is not a proven reaction order.
Its proteins
| Protein | EC | Reaction (UniProt) | Metal or cluster | Amino acids | Certainty |
|---|---|---|---|---|---|
| Lipoyl synthase | 2.8.1.8 | [[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) = [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] | [4Fe-4S] cluster | 276 | Step named |
| lipoate--protein ligase | 6.3.1.20 | L-lysyl-[lipoyl-carrier protein] + (R)-lipoate + ATP = N(6)-[(R)-lipoyl]-L-lysyl-[lipoyl-carrier protein] + AMP + diphosphate + H(+) | — | 345 | Step named |
| BPL/LPL catalytic domain-containing protein | — | — | — | 217 | System only |
| Radical SAM core domain-containing protein | — | — | [4Fe-4S] cluster | 341 | Step named |
| ATP-dependent dethiobiotin synthetase BioD | 6.3.3.3 | (7R,8S)-7,8-diammoniononanoate + CO2 + ATP = (4R,5S)-dethiobiotin + ADP + phosphate + 3 H(+) | Mg(2+) | 220 | Step named |
| biotin--[biotin carboxyl-carrier protein] ligase | 6.3.4.15 | biotin + L-lysyl-[protein] + ATP = N(6)-biotinyl-L-lysyl-[protein] + AMP + diphosphate + H(+) | — | 233 | Step named |
| Biotin synthase | 2.8.1.6 | (4R,5S)-dethiobiotin + (sulfur carrier)-SH + 2 reduced [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine = (sulfur carrier)-H + biotin + 2 5'-deoxyadenosine + 2 L-methionine + 2 oxidized [2Fe-2S]-[ferredoxin] | [4Fe-4S] cluster, [2Fe-2S] cluster | 332 | Step named |
Origins
Could biotin and lipoate, the carriers of carbon dioxide and acyl groups, have been available before cells made them?
Ribozymes found by laboratory selection (Jadhav and Yarus) can make biotinyl-CoA and acetyl-CoA from activated acyl groups and CoA that is tethered to the ribozyme. The researchers supplied the activated reagents.
In the cell, biotin works only when it is attached to a specific lysine of a carrier protein. In E. coli, acetyl-CoA carboxylase uses three separate proteins: the biotin carrier, the enzyme that loads carbon dioxide on it, and the enzyme that passes it on.
Making biotin and lipoate also needs radical chemistry on iron-sulfur clusters. Seven proteins of the minimal set serve these two cofactors.
From the books: Ribas de Pouplana (ed.), The Genetic Code and the Origin of Life, p. 67; Zubay, Origins of Life on Earth and in the Cosmos, p. 336.
The wider question for this part of the cell: origins for manufacturing cofactors and vitamins.
Sources
- Atlas pathway grouping from the VF5 reference-genome system map (Deckert et al. 1998; Braakman & Smith 2014)
Other pathways in this group: Heme and quinones · NAD and flavins · Thiamine and pyridoxal · Folate and pterin chemistry · Lipid and cofactor connections · Coenzyme A · Aspartate-family branches · Amino-acid connections · Folate-linked carbon transfer · Serine, glycine and sulfur · Folate biosynthesis · Oxidative phosphorylation · Thiamine metabolism · Pantothenate and CoA biosynthesis · Glycine, serine and threonine metabolism · Riboflavin metabolism · Nicotinate and nicotinamide metabolism · Biotin metabolism · Cysteine and methionine metabolism · Porphyrin metabolism · Pyruvate metabolism · Not yet placed in a pathway