Anaerobic E. coli lactate-overproduction knockout screen
Domain: biology (systems-biology, metabolic-engineering, constraint-based-modelling)
Topic: Anaerobic E. coli lactate-overproduction knockout screen
Venue: ARC-Bench Biology 2026
Headline metric: primary_metric (maximize)

Research briefing:
Lactate production under anaerobic glucose conditions is a tractable
metabolic-engineering task for constraint-based modelling. A credible study
loads an E. coli BIGG model, validates anaerobic growth, computes WT lactate
secretion, screens central-carbon and fermentation knockouts, and ranks
interventions that increase lactate secretion while preserving growth.

Hypotheses:
statement: The model supports positive anaerobic glucose growth after oxygen uptake is closed., statement: The lactate production envelope shows a tradeoff between biomass growth and maximum lactate secretion., statement: Top lactate-improving knockouts disable competing ethanol, formate, acetate, or succinate by-product routes, or have a specific mechanistic explanation.

Experiment design:
research_question: Which single-gene knockouts increase anaerobic lactate secretion in E. coli while preserving at least 30-50% of WT growth?
conditions: name: wt_anaerobic_glucose
description: E. coli iJO1366 or iAF1260 on glucose-minimal medium with oxygen uptake closed., name: lactate_production_envelope
description: Sweep biomass fraction and optimize lactate secretion., name: single_ko_screen_fermentation
description: Screen central-carbon and fermentation genes; rank by lactate flux at fixed growth fraction.
baselines: Wild-type anaerobic glucose lactate secretion., No-knockout lactate envelope.
metrics: name: anaerobic_wt_growth_1_per_h
direction: maximize
description: WT biomass flux with oxygen uptake set to zero., name: lactate_flux_mmol_gDW_h
direction: maximize
description: Lactate exchange secretion flux., name: lactate_yield_per_glucose
direction: maximize
description: Lactate secretion divided by glucose uptake., name: growth_fraction
direction: threshold
description: KO biomass relative to WT anaerobic growth.
datasets: name: E. coli GSMM
source: BIGG iJO1366 or iAF1260 via cobra.io.load_model
compute_requirements: gpu_required: no
estimated_wall_clock_sec: 1800

Requirements:
type: artifact
description: results.json contains primary_metric, metrics, hypotheses, summary, and top KO structured results., type: numeric
description: Oxygen uptake is explicitly closed and anaerobic WT growth is reported., type: discussion
description: Top 5 lactate-ranked knockouts are reported with gene_id, gene_name, growth_fraction, lactate_flux, and mechanism/canonical flag., type: artifact
description: A biomass-vs-lactate production envelope figure exists with labelled axes and units., type: discussion
description: Each of hypotheses.h1, hypotheses.h2, hypotheses.h3 in results.json MUST have an explicit `supported` boolean and a `details` string of at least 40 characters describing the evidence used to reach that verdict.
, type: discussion
description: Top-3 lactate-improving KO targets are discussed mechanistically — naming the pathway each KO disables and a one-sentence rationale for why the disruption redirects anaerobic flux to lactate. Acceptable inside summary, structured_results, or a separate writeup field., type: discussion
description: The solver backend (cobra optlang interface name + version) and COBRApy version are reported in results.json. Required for reproducibility but not for scientific correctness.

Scoring rubric:
requirements: A credible anaerobic E. coli lactate-overproduction study using COBRApy that validates anaerobic growth, computes a lactate production envelope, screens a focused central-carbon/fermentation knockout set, and explains top candidates mechanistically.
judging_note: Accept iJO1366, iAF1260, or comparable curated E. coli models. Score coherent anaerobic setup and mechanistic KO interpretation over exact gene names.
sub_tasks: requirements: COBRApy code implements anaerobic medium, lactate objective/envelope, and knockout screening.
sub_tasks: requirements: Loads an E. coli BIGG model, sets glucose uptake, closes oxygen uptake, and names biomass and lactate exchange reactions.
task_category: Code Development
finegrained_task_category: Experimental Setup, requirements: Computes biomass-vs-lactate production envelope by constraining biomass fractions and optimizing or FVA-bounding lactate secretion.
task_category: Code Development
finegrained_task_category: Method Implementation, requirements: Screens a focused set of no more than 100 central-carbon and fermentation genes with model state restored between knockouts.
task_category: Code Development
finegrained_task_category: Method Implementation, requirements: Computes lactate yield as lactate secretion divided by absolute glucose uptake, separate from flux.
task_category: Code Development
finegrained_task_category: Method Implementation, requirements: Execution produces valid anaerobic WT, envelope, and KO tables.
sub_tasks: requirements: WT anaerobic FBA is optimal with positive biomass and at least 85% of KO simulations solve or are explicitly labelled infeasible/lethal.
task_category: Code Execution
finegrained_task_category: Evaluation, Metrics & Benchmarking, requirements: Mass-balance check passes for the loaded anaerobic model; no aerobic by-products (O2 uptake or CO2 via respiration) appear under strictly anaerobic conditions without explanation; biomass flux is positive under anaerobic glucose reference. This is the biology-validity gate equivalent to physics-validity checks in the physics rubric.
task_category: Code Execution
finegrained_task_category: Evaluation, Metrics & Benchmarking, requirements: Writes results.json plus machine-readable envelope and KO-ranking tables.
task_category: Code Execution
finegrained_task_category: Logging, Analysis & Presentation, requirements: Results quantify lactate production, growth tradeoffs, and KO mechanisms.
sub_tasks: requirements: Reports anaerobic WT growth and confirms oxygen uptake is zero or bounded closed. Score 100% if positive anaerobic WT biomass flux is reported with O2 exchange confirmed ≤0 mmol/gDW/h; 67% if growth is positive but O2 status is not explicitly confirmed; 33% if anaerobic feasibility is stated without a numeric growth value; 0% otherwise.
task_category: Result Analysis
finegrained_task_category: Logging, Analysis & Presentation, requirements: Shows lactate secretion changes across biomass fractions and identifies whether production is growth-coupled, competing, or partially coupled. Score 100% if lactate secretion flux is non-decreasing as biomass fraction decreases across ≥8 of 10 envelope grid points; 67% if non-decreasing over ≥6 of 10 points; 33% if ≥4 of 10 points; 0% otherwise.
task_category: Result Analysis
finegrained_task_category: Logging, Analysis & Presentation, requirements: Top 5 KO list includes growth fraction, lactate flux/yield, and pathway-level rationale for at least top 3 targets. Score 100% if ≥3 of the top-5 KOs disrupt canonical competing by-product pathways (acetate, ethanol, formate, or succinate routes) or include a specific mechanistic explanation; 67% if 2 of 5 meet this criterion; 33% if 1 of 5; 0% otherwise.
task_category: Result Analysis
finegrained_task_category: Logging, Analysis & Presentation, requirements: Produces a labelled lactate envelope or KO ranking figure with units.
task_category: Result Analysis
finegrained_task_category: Logging, Analysis & Presentation, requirements: The README or results writeup discusses each hypothesis outcome, names the top lactate-improving knockouts with their gene/enzyme identity, and gives a one-paragraph mechanistic interpretation (which competing pathways the KOs disable, why this redirects anaerobic flux to lactate).
task_category: Result Analysis
finegrained_task_category: Logging, Analysis & Presentation, requirements: Medium, model, gene set, solver, and thresholds are reproducibly recorded.
sub_tasks: requirements: The loaded E. coli GSMM is either persisted (models/<model_id>.json) or pinned by BIGG model ID and source URL in the writeup; a downstream user can locate the exact model object and reproduce the anaerobic medium setup.
task_category: Code Development
finegrained_task_category: Reproducibility, requirements: Saves anaerobic medium bounds, biomass threshold, KO gene set, and lactate reaction ID.
task_category: Code Development
finegrained_task_category: Reproducibility, requirements: Records COBRApy/solver versions and confirms rerun consistency for WT growth.
task_category: Code Development
finegrained_task_category: Reproducibility