Fig. 6. Application of synthetic co-cultures for improved resveratrol production.

a, De novo resveratrol synthesis pathway in yeast and diagram of division of labour of resveratrol pathway in yeast cross-feeding co-cultures. b–d, Global sensitivity analysis of a division of labour biotechnological process. The model and full results are discussed in Supplementary Note 4. Model parameters are as follows: ϕ_i, the proportion of glucose flux going to production of metabolite i by strain y_i; $x_{0,i}$, the initial concentration of metabolite i in the medium; $r_{0,i}$, the initial starting population of strain i (note that $r_{\mathrm{0,1}}+r_{\mathrm{0,2}}=1$); $V_{\max ,G}^{y_i}$, the maximum uptake rate of glucose G by strain y_i; $V_{\max ,j}^{y_i}$, the maximum uptake rate of metabolite j by strain y_i; δ is the dummy parameter used for statistical tests in the global sensitivity analysis as described in Methods. Shown are the sensitivities of the final OD₇₀₀ (b), the pathway productivity (c) and the pathway yield ratio (d) to key parameters. Asterisk indicates sensitivity or total sensitivity is significantly different (P < 0.01) from the dummy parameter (see Supplementary Note 4 for full analysis). e,f, OD₇₀₀ values (e) (calculated using Supplementary Table 9 for consistency) and resveratrol concentrations (f) of the seven pairs of co-cultures and the monoculture control (Mctrl) at 48 h in synthetic minimal medium. The co-culture setup and remaining p-coumaric acid concentrations in synthetic co-cultures are shown in Supplementary Fig. 32. N = 3 biologically independent samples and data are presented as mean ± s.d. Two-way ANOVA, followed by Turkey’s multiple comparisons test with 95% confidence intervals were performed using GraphPad Prism 9.5.0 and P values are noted.

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