Journal
FEMS MICROBIOLOGY LETTERS
Volume 365, Issue 15, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/femsle/fny164
Keywords
Cyanobacteria; secondary metabolites; Anabaena sp strain PCC 7120; promoter
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Funding
- College of Pharmacy, Oregon State University
- Medical Research Foundation of Oregon [1415]
- AREA award grant from the National Institutes of Health [1R15GM117541-01A1]
- Professional Development Award from the Oregon State Postdoctoral Association
- Honors Experience Scholarship from the University Honors College
- Undergraduate Summer Research Scholarship from the College of Pharmacy
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Cyanobacterial natural products offer new possibilities for drugs and lead compounds but many factors can inhibit the production of sufficient yields for pharmaceutical processes. While Escherichia coil and Streptomyces sp. have been used as heterologous expression hosts to produce cyanobacterial natural products, they have not met with resounding success largely due to their inability to recognize cyanobacterial promoter regions. Recent work has shown that the filamentous freshwater cyanobacterium Anabaena sp. strain PCC 7120 recognizes various cyanobacterial promoter regions and can produce lyngbyatoxin A from the native promoter. Introduction of Anabaena sigma factors into E. coli might allow the native transcriptional machinery to recognize cyanobacterial promoters. Here, all 12 Anabaena sigma factors were expressed in E. coli and subsets were found to initiate transcription from several cyanobacterial promoters based on transcriptional fusions to the chloramphenicol acetyltransferase (CAT) reporter. Expression of individual Anabaena sigma factors in E. coil did not result in lyngbyatoxin A production from its native cyanobacterial gene cluster, possibly hindered by deficiencies in recognition of cyanobacterial ribosomal binding sites by native E. coli translational machinery. This represents an important step toward engineering E. coli into a general heterologous expression host for cyanobacterial biosynthetic gene cluster expression.
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