Process Engineering Strategies for Microbial Lipid Production: From Strain Evolution to Industrial-Scale Bioprocessing.

Microbial lipids have emerged as a promising sustainable alternative to plant- and petroleum-derived oils, with applications spanning biofuels, oleochemicals, nutraceuticals, and specialty materials. Significant advances in metabolic engineering and strain development have increased lipid production capacity across diverse microorganisms. Numerous reviews have summarized the biological and metabolic advances in this field, highlighting significant progress in metabolic engineering and strain development that has increased lipid production capacity across diverse microorganisms. However, translating these gains into economically viable industrial processes remains a major challenge. This review examines process engineering strategies for microbial lipid production across the full bioprocessing pipeline, from laboratory-scale strain evolution to industrial-scale operation. We discuss recent developments in adaptive laboratory evolution, systems-guided strain optimization, and robustness engineering, emphasizing their implications for process performance. Key bioprocess parameters-including substrate selection, nutrient limitation strategies, reactor design, oxygen transfer, and process control-are critically evaluated for their impact on lipid yield, productivity, and scalability. Furthermore, downstream processing considerations and techno-economic constraints are analyzed in the context of large-scale implementation. By integrating strain-level innovations with process engineering principles, this review highlights current bottlenecks, emerging solutions, and future directions for achieving efficient and scalable microbial lipid biomanufacturing.