Engineering by evolution

F Arnold
Engineering by evolution

• Follow up : where to explore?
• Nature is the best engineer
• Genome is composed like heavenly music
• We are not making music we just make pieces and it will become music
• We dont understand seq to fxn
• Protein folding is not understood
• Evolution does it very well

1. Algorithm to create or modify new forms of life to solve human problems

• Physically possible proteins
• We are looking at proteins relevant to biology only
• Small fractions
• Evolution is hard
• 450 aa protein with 20 aa types
• 20 to the power 450
• Directed evolution exploits smooth paths in fitness landscape
• Parent gene 10(15) via cells 10(7)select 10(4) if yes ---evolved gene repeat the process
• Favorite protein CYTOCHROME P450 selective insertion of O2 into unactivated C-H bonds at room temp
• Converts gas alkanes into alcohols
• Cytochrome p411
• Enz is highly evolvable
• Many beneficial muations are far from active sites
• Details matters they are important
• We dont understand the details

2. Recombination is conservative

• Chimeras
• Chimeric Proteins fxnal if parental seq are similar
• Swattable elements of proteins
• Recombination is innovative
• Bacterial enzymes novel recombonation p450
• Linear regression
• Even can improve cellulase

Next : minerals in mix. Novel aa
Learn the rules pf the best designer: nature







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