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Introduction: Syngas, a mixture of H2, CO and CO2, can be generated from a wide range of (low-biodegradable wastes) and is a suitable feedstock for biotechnological processes. Several microorganisms are able to use syngas for growth, but main natural products from this fermentation are acetate and ethanol. In order to extend the range of products from syngas fermentation, we constructed a synthetic co-culture of Clostridium autoethanogenum, a carboxydotrophic acetogen, with Clostridium kluyveri, a bacterium employing the reverse -oxidation pathwaya. C. autoethanogenum converted syngas to acetate and ethanol, and C. kluyveri elongated these products to butyrate and caproate. Methods: Experiments in batch bottles and chemostats were conducted to study the differences in physiological behavior between monocultures of C. autoethanogenum and co-cultures of C. autoethanogenum and C. kluyveri. In addition to physiological characterization a transcriptomics approach was used to unravel the molecular functioning of this co-cultureb. Results: Expression of the central carbon- and energy-metabolism of C. autoethanogenum in pure or in co-culture with C. kluyveri remained unaltered. However, the electron flux from CO to intermediate products (acetate/ethanol) was substantially shifted towards the production of ethanol. In co-culture conditions fed with additional acetate, the metabolism of C. autoethanogenum could be pushed to produce only ethanol from CO, resulting in high yields of chain elongated acids by the co-culture. Conclusions: The results suggest that thermodynamics and metabolic dependence between the two strains, rather than gene expression, plays a key role in the ratio of products formed during CO fermentation by C. autoethanogenum. Overall this suggests that microbial interactions can be exploited to steer the syngas fermentation process towards products of interest, enhancing both the efficiency and the products spectrum of syngas fermentation technology., info:eu-repo/semantics/publishedVersion