Shafaei, S. | Search bioRxiv

bioRxiv2026

An AI-powered cloud biofoundry for autonomous biological research

Autonomous experimentation, where an automated system designs, performs, analyzes, and iteratively improves experiments with minimal human intervention represents a transformative scientific research paradigm. However, it remains hampered by the disconnect between computational design and experimental execution. Here we present iCloudBiofoundry, a cloud-accessible, scalable, and self-evolving platform that bridges this divide. A scientific multi-agent system, iBioGenie, plans research workflows by converting natural language research objectives into testable hypotheses and experimentally grounded protocols using literature, databases, and computational tools. A physical AI layer, BiofoundryAI, translates them into executable workflows that run autonomously on distributed robotic biofoundries, and collects the data for iterative design. We demonstrate the end-to-end capabilities of iCloudBiofoundry across three representative case studies spanning enzyme retrieval, protein engineering, and metabolic engineering. By integrating agentic AI with physical AI, iCloudBiofoundry provides a cloud accessible platform that unifies computational design and robotic execution, enabling autonomous biological research.

synthetic biology↗

bioRxiv2023

An end-to-end pipeline for succinic acid production at an industrially relevant scale using Issatchenkia orientalis

As one of the top value-added chemicals, succinic acid has been the focus of numerous metabolic engineering campaigns since the 1990s. However, microbial production of succinic acid at an industrially relevant scale has been hindered by high downstream processing costs arising from neutral pH fermentation. Here we describe the metabolic engineering of Issatchenkia orientalis, a non-conventional yeast with superior tolerance to highly acidic conditions, for cost-effective succinic acid production. Through deletion of byproduct pathways, transport engineering, and expanding the substrate scope, the resulting strains could produce succinic acid at the highest titers in sugar-based media at low pH (pH 3) in fed-batch fermentations using bench-top reactors, i.e. 109.5 g/L in minimal medium and 104.6 g/L in sugarcane juice medium. We further performed batch fermentation in a pilot-scale fermenter with a scaling factor of 300x, achieving 63.1 g/L of succinic acid using sugarcane juice medium. A downstream processing comprising of two-stage vacuum distillation and crystallization enabled direct recovery of succinic acid, without further acidification of fermentation broth, with an overall yield of 64.0%. Finally, we simulated an end-to-end low-pH succinic acid production pipeline, and techno-economic analysis and life cycle assessment indicate our process is financially viable and can reduce life cycle greenhouse gas emissions by 34-90% relative to fossil-based production processes. We expect I. orientalis can serve as a general industrial platform for the production of a wide variety of organic acids.

synthetic biology↗