biostudies-literatureHeng YCNational Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)National University of SingaporeAgency for Science, Technology and Research (A*STAR)Agency for Science, Technology and ResearchNational Research Foundation SingaporeNational University of Singapore (NUS)8163https://www.ebi.ac.uk/biostudies/studies/S-EPMC11408693biostudies-literatureUnknown15(1)This study introduces a synthetic biology approach that reprograms the yeast mating-type switching mechanism for tunable cell differentiation, facilitating synthetic microbial consortia formation and cooperativity. The underlying mechanism was engineered into a genetic logic gate capable of inducing asymmetric sexual differentiation within a haploid yeast population, resulting in a consortium characterized by mating-type heterogeneity and tunable population composition. The utility of this approach in microbial consortia cooperativity was demonstrated through the sequential conversion of xylan into xylose, employing haploids of opposite mating types each expressing a different enzyme of the xylanolytic pathway. This strategy provides a versatile framework for producing and fine-tuning funcNature communicationsTunable cell differentiation via reprogrammed mating-type switching.PMC11408693NRF-MSG-2023-0003NUHSRO/2020/077/MSC/02/SBNRF-NRFI05-2019-0004NRF-CRP27-2021-0004I2301E0021Heng YCSusanto AVKitano SFoo JLChang MWfalseTunable cell differentiation via reprogrammed mating-type switching.This study introduces a synthetic biology approach that reprograms the yeast mating-type switching mechanism for tunable cell differentiation, facilitating synthetic microbial consortia formation and cooperativity. The underlying mechanism was engineered into a genetic logic gate capable of inducing asymmetric sexual differentiation within a haploid yeast population, resulting in a consortium characterized by mating-type heterogeneity and tunable population composition. The utility of this approach in microbial consortia cooperativity was demonstrated through the sequential conversion of xylan into xylose, employing haploids of opposite mating types each expressing a different enzyme of the xylanolytic pathway. This strategy provides a versatile framework for producing and fine-tuning func2024-01-01T00:00:00Z2024 Sep2026-06-03T00:03:12.246Z2025-04-04T08:18:05.273ZS-EPMC114086933928934610.1038/s41467-024-52282-w