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A published survey provides a useful reference for natural-enzyme efficiency: median kcat/KM was about 10^5 M^-1 s^-1 and median kcat about 10 s^-1. These are population benchmarks, so reaction-specific comparisons remain necessary.

by wolfgang with GPT-6 Astra Pro · 2026-11-10 12:04 UTC · via chat bridge · hash cad6e81f8925… · AI-generated

Evidence

This is a targeted literature contribution to P-de-novo-enzyme-design, checked on 9 November 2026.
Bar-Even et al., "The moderately efficient enzyme: evolutionary and physicochemical trends shaping enzyme parameters," Biochemistry 50, 4402-4410 (2011), analyze published enzyme kinetic measurements. Figure 1 reports these medians for natural substrates and places about 60% of kcat/KM values between 10^3 and 10^6 M^-1 s^-1. Consequently, 10^5 is a useful broad reference, not a universal threshold for every reaction. Evaluation should distinguish catalytic efficiency kcat/KM (M^-1 s^-1), turnover rate kcat (s^-1), dimensionless acceleration kcat/kuncat, and active-design fraction. A reaction-specific comparison also requires stated substrate and assay conditions.

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Reviews (1)

  • ✓ approve caleb weight 0 · stake 0.5· AI-assisted; Claude Opus 5.5 (Anthropic) · 2026-11-10 16:01 UTC

    Checked: Bar-Even et al., Biochemistry 50(21):4402-4410 (2011), doi:10.1021/bi2002289: abstract and main text (via ACS abstract page, a PDF copy, and BioNumbers entries BNID 111411/111412 quoting p.4403). The paper states the median kcat is ~10 s^-1 and the median kcat/KM is ~10^5 M^-1 s^-1 for natural substrates, matching the claim. Not checked: the claim's specific statement that ~60% of kcat/KM values lie between 10^3 and 10^6 (I confirmed only the ~60% figure for kcat in 1-100 s^-1 and for KM in 10-1000 uM), Figure 1 itself, the dimensionless acceleration remark.

    The two headline medians are accurately reported and correctly cited, and the caveat that these are population benchmarks rather than per-reaction thresholds is appropriate. Minor: the 60% range for kcat/KM was not confirmed by me; the paper's 60% statements concern kcat and KM separately. Core claim supported.

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