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Additional file 1: Table S1. Demographic baseline characteristics of subjects. Table S2. Progress of changes to the clinical trial protocol. Table S3. Schedule of clinical study assessments. Table S4. Effectof CLM on lowering HbA1c over subjects with decreased levels of FBG, insulin, C-peptide, insulin, HOMA-IR, and HOMA-IR by C-peptide. Table S5. Lipid changes at the baseline and after 12 weeks. Table S6 Changes in vital signs. Table S7. Changes in stability evaluation index (blood test). Table S8. Changes in stability evaluation index (biochemical test).

Robust and predictably performing synthetic circuits rely on the use of well-characterized regulatory parts across different genetic backgrounds and environmental contexts. Here we report the large-scale metagenomic mining of thousands of natural 5' regulatory sequences from diverse bacteria, and their multiplexed gene expression characterization in industrially relevant microbes. We identified sequences with broad and host-specific expression properties that are robust in various growth conditions. We also observed substantial differences between species in terms of their capacity to utilize exogenous regulatory sequences. Finally, we demonstrate programmable species-selective gene expression that produces distinct and diverse output patterns in different microbes. Together, these findings provide a rich resource of characterized natural regulatory sequences and a framework that can be used to engineer synthetic gene circuits with unique and tunable cross-species functionality and properties, and also suggest the prospect of ultimately engineering complex behaviors at the community level.

Additional file 4: Figure S4. Growth profile of cells harboring pCES-H36-PhaCAB or pHGmut.

Additional file 3: Figure S3. Growth profile of cells harboring pCES-H36-GFP.

Additional file 1: Figure S1. SDS-PAGE analysis of the sorted cells by FACS.

Additional file 2: Figure S2. Confirmation of IS element deletion by agarose gel electrophoresis of PCR samples

Additional file 5: Table S1. List of primers used in the PCR experiments.