Solution - A to Zecora

By Nishant Pappireddi

Each of the chemical reactions in the cheat sheet is a real-world synthesis reaction for a certain amino acid, except the amino acid product has been replaced by a different, incorrect, amino acid. The synthesis reactions are as follows:

    Homocysteine + Levomefolic Acid → Methionine (replaced by Aspartic Acid) + Tetrahydrofolic Acid

    Valine + 3-Methyl-2-oxovalerate → 3-Methyl-2-oxobutanoic acid + Isoleucine (replaced by Phenylalanine)

    Glutamine + Aspartic Acid → Glutamic Acid + Asparagine (replaced by Glycine)

    Indole + Serine → Tryptophan (replaced by Histidine)

    α-ketoglutarate → Glutamic Acid (replaced by Lysine)

    (Hydrated Acyclic Precursor) → Pyrrolysine (replaced by Leucine)

    Argininosuccinic Acid → Arginine (replaced by Proline) + Fumaric Acid

    Glutamic Acid + Pyruvate → α-ketoglutaric acid + Alanine (replaced by Glutamine)

    Cystathionine → Cysteine (replaced by Selenocysteine) + α-ketobutyric acid

    Phosphoserine → Serine (replaced by Valine)

    Phosphohomoserine → Threonine (replaced by Tyrosine)

Each amino acid can be converted to an English letter through the IUPAC code. As stated in the flavor, on top of the central dogma of 20 amino acids, the puzzle also uses two more unusual proteinogenic amino acids: Selenocysteine, with symbol U, and Pyrrolysine, with symbol O. The reactions are ordered by alphabetically by the letter for the incorrect amino acid.

The provided sequence of letters is an mRNA strand, which can be divided into codons of 3 bases, converted to an amino acid, then converted to letters. Some care needs to be taken here, since the unusual amino acids are encoded by two of the three regular stop codons (Selenocysteine by UGA and Pyrrolysine by UAG). With this modification to the usual genetic code, the mRNA sequence translates to the following sequence of peptides (dashes are stop codons):


Aside from the obligatory M's from start codons, all the amino acids are the incorrect ones which have replaced the correct synthesis products in the reactions. We can treat the reactions as a substitution cipher, mapping incorrect amino acids to correct ones.

Incorrect Amino Acid Letter Letter Correct Amino Acid
Aspartic Acid D M Methionine
Phenylalanine F I Isoleucine
Glycine G N Asparagine
Histidine H W Tryptophan
Lysine K E Glutamic Acid
Leucine L O Pyrrolysine
Proline P R Arginine
Glutamine Q A Alanine
Selenocysteine U C Cysteine
Valine V S Serine
Tyrosine Y T Threonine
If we substitute the correct amino acids instead, the sequence of peptides becomes:


Ignoring the M's (the start codons), this gives the words "C TERM TO N TERM REWSNA NOITCARTTA" Since proteins are usually written from N-term to C-term, the phrase "C TERM TO N TERM" means that the final two words should be read backwards, giving "ANSWER ATTRACTION." Thus, the answer is ATTRACTION.

Authors Notes

I wanted to use an mRNA sequence and the resulting translated sequence of peptides to give a cluephrase, so I decided to make a substitution cipher using the 22 proteinogenic amino acids (Pyrrolysine and Selenocysteine give access to the letters O and U, making cluephrase construction easier). I then came up with the idea of writing chemical reactions involving the amino acids and performing a substitution cipher on them. Then I could make the mRNA sequence translate to the ciphertext of the cluephrase. I made cluephrase resulting from the translated mRNA partially backwards to prevent it from being solved by a cryptogram solver.

The original version of this puzzle had 22 reactions, depicting a full permutation of the 22 amino acids, but that ended up being too long, so I reduced it to 11 reactions, showing 11 "plaintext" amino acids being replaced by 11 "ciphertext" amino acids. Some of the reactions above involve other amino acids besides the one being synthesized, and I originally had those ones also replaced by their ciphertext versions, but that also was too convoluted, so the final version kept these amino acids the same.