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The eight-carbon fatty acid octanoic acid (OA) is an important platform chemical and precursor of many industrially relevant products. Its microbial biosynthesis is regarded as a promising alternative to current unsustainable production methods. In Saccharomyces cerevisiae, the production of OA had been previously achieved by rational engineering of the fatty acid synthase. For the supply of the precursor molecule acetyl-CoA and of the redox cofactor NADPH, the native pyruvate dehydrogenase bypass had been harnessed, or the cells had been additionally provided with a pathway involving a heterologous ATP-citrate lyase. Here, we redirected the flux of glucose towards the oxidative branch of the pentose phosphate pathway and overexpressed a heterologous phosphoketolase/phosphotransacetylase shunt to improve the supply of NADPH and acetyl-CoA in a strain background with abolished OA degradation. We show that these modifications lead to an increased yield of OA during the consumption of glucose by more than 60% compared to the parental strain. Furthermore, we investigated different genetic engineering targets to identify potential factors that limit the OA production in yeast. Toxicity assays performed with the engineered strains suggest that the inhibitory effects of OA on cell growth likely impose an upper limit to attainable OA yields.

Octanoic acid is an industrially relevant compound with applications in antimicrobials or as a precursor for biofuels. Microbial biosynthesis through yeast is a promising alternative to current unsustainable production methods. To increase octanoic acid titers in Saccharomyces cerevisiae, we use a previously developed biosensor that is based on the octanoic acid responsive pPDR12 promotor coupled to GFP. We establish a biosensor strain amenable for high-throughput screening of an octanoic acid producer strain library. Through development, optimization, and execution of a high-throughput screening approach, we were able to detect two new genetic targets, KCS1 and FSH2, which increased octanoic acid titers through combined overexpression by about 55% compared to the parental strain. Neither target has yet been reported to be involved in fatty acid biosynthesis. The presented methodology can be employed to screen any genetic library and thereby more genes involved in improving octanoic acid production can be detected in the future.

Octanoic acid is an industrially relevant compound with applications in antimicrobials or as a precursor for biofuels. Microbial biosynthesis through yeast is a promising alternative to current unsustainable production methods. To increase octanoic acid titers in

A sustainable production of pharmaceuticals, chemicals, and biofuels is indispensable for an environmentally friendly future. Many of these compounds are based on fatty acids and their derivatives, generically referred to as oleochemicals. As an alternative to both petrochemistry and extraction from oil plants, modern approaches focus on engineering microbes for production of oleochemicals from biomass. This review describes strategies developed in Saccharomyces cerevisiae, a eukaryotic host in which substantial advances in the production of oleochemicals have been very recently achieved through a combination of metabolic engineering and optimized fermentation regimes. The survey of the available literature shows that model-based pathway optimization holds promise to enable an economically feasible production of oleochemicals in the near future.

Short- and medium-chain fatty acids (SMCFA) are important platform chemicals currently produced from nonsustainable resources. The engineering of microbial cells to produce SMCFA, however, lacks high-throughput methods to screen for best performing cells. Here, we present the development of a whole-cell biosensor for easy and rapid detection of SMCFA. The biosensor is based on a multicopy yeast plasmid containing the SMCFA-responsive PDR12 promoter coupled to GFP as the reporter gene. The sensor detected hexanoic, heptanoic and octanoic acid over a linear range up to 2, 1.5, and 0.75 mM, respectively, but did not show a linear response to decanoic and dodecanoic acid. We validated the functionality of the biosensor with culture supernatants of a previously engineered Saccharomyces cerevisiae octanoic acid producer strain and derivatives thereof. The biosensor signal correlated strongly with the octanoic acid concentrations as determined by gas chromatography. Thus, this biosensor enables the high throughput screening of SMCFA producers and has the potential to drastically speed up the engineering of diverse SMCFA producing cell factories.

In this work, we present a comprehensive analysis of the H3K36 histone methyltransferases Set2 and Ash1 in the filamentous ascomycete Fusarium fujikuroi. In Saccharomyces cerevisiae, one single methyltransferase, Set2, confers all H3K36 methylation, while there are two members of the Set2 family in filamentous fungi, and even more H3K36 methyltransferases in higher eukaryotes. Whereas the yeast Set2 homolog has been analyzed in fungi previously, the second member of the Set2 family, designated Ash1, has not been described for any filamentous fungus. Western blot and ChIP-Seq analyses confirmed that F. fujikuroi Set2 and Ash1 are H3K36-specific histone methyltransferases that deposit H3K36me3 at specific loci: Set2 is most likely responsible for H3K36 methylation of euchromatic regions of the genome, while Ash1 methylates H3K36 at the subtelomeric regions (facultative heterochromatin) of all chromosomes, including the accessory chromosome XII. Our data indicate that H3K36me3 cannot be considered a hallmark of euchromatin in F. fujikuroi, and likely also other filamentous fungi, making them different to what is known about nuclear characteristics in yeast and higher eukaryotes. We suggest that the H3K36 methylation mark exerts specific functions when deposited at euchromatic or subtelomeric regions by Set2 or Ash1, respectively. We found an enhanced level of H3K27me3, an increased instability of subtelomeric regions and losses of the accessory chromosome XII over time in Δash1 mutants, indicating an involvement of Ash1 in DNA repair processes. Further phenotypic analyses revealed a role of H3K36 methylation in vegetative growth, sporulation, secondary metabolite biosynthesis, and virulence in F. fujikuroi.

In this work, we present a comprehensive analysis of the H3K36 histone methyltransferases Set2 and Ash1 in the filamentous ascomycete Fusarium fujikuroi. In Saccharomyces cerevisiae, one single methyltransferase, Set2, confers all H3K36 methylation, while there are two members of the Set2 family in filamentous fungi, and even more H3K36 methyltransferases in higher eukaryotes. Whereas the yeast Set2 homolog has been analyzed in fungi previously, the second member of the Set2 family, designated Ash1, has not been described for any filamentous fungus. Western blot and ChIP-Seq analyses confirmed that F. fujikuroi Set2 and Ash1 are H3K36-specific histone methyltransferases that deposit H3K36me3 at specific loci: Set2 is most likely responsible for H3K36 methylation of euchromatic regions of the genome, while Ash1 methylates H3K36 at the subtelomeric regions (facultative heterochromatin) of all chromosomes, including the accessory chromosome XII. Our data indicate that H3K36me3 cannot be considered a hallmark of euchromatin in F. fujikuroi, and likely also other filamentous fungi, making them different to what is known about nuclear characteristics in yeast and higher eukaryotes. We suggest that the H3K36 methylation mark exerts specific functions when deposited at euchromatic or subtelomeric regions by Set2 or Ash1, respectively. We found an enhanced level of H3K27me3, an increased instability of subtelomeric regions and losses of the accessory chromosome XII over time in Δash1 mutants, indicating an involvement of Ash1 in DNA repair processes. Further phenotypic analyses revealed a role of H3K36 methylation in vegetative growth, sporulation, secondary metabolite biosynthesis, and virulence in F. fujikuroi.

We explore the dynamics of demand for n designs of a good when agents have preferences for (anti-)conformity. Agents differ in their social status and each agent seeks to imitate those of higher status and to distinguish herself from those of lower status, relative to her own status. In each period, every agent chooses a design given each agent's demand in the previous period. We show that demand dynamics resemble fashion cycles: The demand for designs is repetitively bell-shaped over time, and, when positively demanded, a design trickles from high- to low-status individuals. At least for n = 3 , the demand dynamics converge to a unique limit cycle. We obtain a similar (though weaker) convergence result for n = 4 , and simulations suggest that the result holds for n = 4 and 5.

This paper develops a mechanism for a principal to assign a prize to the most valuable agent from a set of heterogeneously valued agents on a network. The principal does not know the value of any agent. Agents are competing for the prize and they have a "knowledge network": If two agents are linked, they know each other's value for the principal. Each agent sends a costless private message to the principal about her own value and the values of other agents she knows. This message can be truthful or not. However, it is common knowledge that agents can lie about each value only to a certain extent and that agents only lie if lying increases their chances of being selected, otherwise they report truthfully. It is shown that the principal - taking advantage of this knowledge - can design a mechanism which defines the selection probability for each agent for each possible message profile such that there exists an equilibrium in which the most valuable agent is selected with certainty.

Often a network is characterized not only by who is linked to whom but also by the intensity of the links. We analyze a network formation model in which homogenous agents have a limited resource (e.g. time) which they can use to form links of possibly different intensity with other agents (e.g. friendships) and which they can invest into themselves. We show that in equilibrium an agent either has no links, belongs to a "reciprocal" component or to a "non-reciprocal" component (maximal connected subgraph of the network). In a reciprocal component, any two agents invest equally into their link and self-investment is identical across the group. In a non-reciprocal component, every agent is either a "high intensity" agent or a "low intensity" agent. High intensity agents are only linked to low intensity agents and vice versa. A high intensity agent always invests more into a link than her counterpart low intensity agent and also chooses a higher self-investment. We show that in equilibrium any component in which every agent has the same number of links must be reciprocal; any component of more than two agents in which at least one agent has only one link must be non-reciprocal. Welfare-maximizing components are reciprocal but feature a lower self-investment than in reciprocal equilibrium because of positive externalities from link investments.

Interdisziplinare Sichtweise und die Kooperation unterschiedlicher Wissenschaftszweige sind in allen gesellschaftlichen Bereichen unerlasslich geworden. So war der Wunsch einiger Initiatorinnen der ifu durchaus nahe liegend, auch die kunstlerischen Disziplinen in den dreimonatigen Hochschulbetrieb der Internationalen Frauenuniversitat einzubeziehen. Im Vergleich mit Erfahrungen bei der Zusammenarbeit anderer wissenschaftlicher Fachgebiete wurde die Beteiligung der Kunste zu einem besonderen experimentellen Prozess, weil es hierzu weder Erfahrungen gibt, auf die man hatte zuruckgreifen konnen, noch der zeitliche Raum zur Verfugung stand, sich auf eine Zusammenarbeit vorzubereiten und allen Beteiligten die Moglichkeit einzuraumen, sich auf die unterschiedlichen Herangehensweisen von Wissenschaftlerinnen und Kunstlerinnen einzulassen.