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Throughout their lifetime, critical infrastructure networks are exposed to risks from external hazards and threats, such as natural hazards, terrorist attacks, and cyber-attacks. Since modern urban infrastructure systems are highly interdependent on each other, the risks of infrastructure failures due to extreme events are far more extensive in geographic scale and intensity. Given that traditional resource allocation methods are based primarily on the performance of individual infrastructure facilities without considering interdependencies among them, the resulting resilience of the infrastructure network is not always optimal. In this study, methodological frameworks are proposed to allocate resources (budget or personnel) to improve the resilience of the infrastructure network considering interdependencies among infrastructure systems. Taking advantage of Agent-Based Modeling (ABM) technique, the proposed methodology frameworks are able to assess the interdependent effects of extreme events and resource allocation strategies. By simulating the interdependent effects with ABM and using the results as inputs to the optimization process, the optimization process for maximizing the infrastructure network resilience is improved. Specifically, the objectives of this study include: 1) maximizing the robustness of the infrastructure network before an extreme event; 2) optimizing the repair crew allocation after an extreme event; and 3) optimizing the long-term infrastructure network resilience when the infrastructure network is potentially subject to multiple occurrences of extreme events. The proposed methodology frameworks are applied to simplified networks consisting of different critical infrastructure systems in order to understand the applicability of the frameworks. The results show that the proposed frameworks are effective in quantifying the interdependent effects of the infrastructure network and improving its resilience.

Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic in human history and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, its biosynthetic mechanisms have remained a long-standing mystery. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and β-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB′ as the long-sought key enzyme responsible for the oxidative cleavage of sesquiterpene side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC and O-methyltransferase MpaG, the Golgi apparatus-associated prenyltransferase MpaA, the endoplasmic reticulum-bound oxygenase MpaB and P450-hydrolase fusion enzyme MpaDE, and the peroxisomal acyl-CoA hydrolase MpaH. The whole pathway is elegantly co-mediated by these compartmentalized enzymes, together with the peroxisomal β-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic pathway, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis.