5-Aminolevulinic acid (5-ALA) is the key precursor for the biosynthesis of tetrapyrrole compounds, with wide applications in medicine, agriculture and other burgeoning fields. Because of its potential applications and disadvantages of chemical synthesis, alternative biotechnological methods have drawn increasing attention. In this review, the recent progress in biosynthetic pathways and regulatory mechanisms of 5-ALA synthesis in biological hosts are summarized. The research progress on 5-ALA biosynthesis via the C4/C5 pathway in microbial cells is emphasized, and the corresponding biotechnological design strategies are highlighted and discussed in detail. In addition, the detection methods and applications of 5-ALA are also reviewed. Finally, perspectives on potential strategies for improving the biosynthesis of 5-ALA and understanding the related mechanisms to further promote its industrial application are conceived and proposed.

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Train timetables are usually established far in advance of operations and are based on forecasted demands. However, due to changes in actual freight traffic, railways need to determine the actual operation of trains arising in daily operations through train path selection, i.e., selecting a portion of the timetable for these trains to execute. To improve current freight train scheduling in daily operations, this paper suggests taking into account the car flow transfer between consecutive trains and shipment delivery time requirements. A train path selection optimization model is developed to minimize the total travel time of freight trains while seeking minimum penalties for shipment delivery delays. A tabu search algorithm is designed to solve this problem. The effectiveness of the proposed model and algorithm is demonstrated by numerical experiments on instances built on real data from the Menghua railway, a rail freight corridor. The results show that, compared to current practice, this optimization method can achieve a reduction in total train travel time and ensure the punctual delivery of shipments.INDEX TERMS Freight transport, train scheduling, tabu search, daily operations.