Biosynthesis of actinoallolide analogs by genetic manipulation

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18888
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Natural medicines
• Research Institution: Kitasato University
• Principal Investigator: Yuki Inahashi 北里大学, 感染制御科学府, 特任助教 (70645522)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: actinoallolide / heterologous expression / trypanosoma

Outline of Final Research Achievements

Actinoallolides are anti-trypanosomal macrolides isolated from the endophytic actinomycetes, Actinoallomurus fulvus MK10-036 and K09-0307. A putative actinoallolide biosynthetic gene cluster was predicted from the genome sequence of the strain K09-0307. The gene cluster was assembled in a BAC vector using Gibson Assembly and ermE* promoter was inserted upstream from the start codon of the polyketide synthase gene. The resulting vector is introduced into S. coelicolor M1152. Subsequent LC/MS analysis identified actinoallolide A in the culture broth. Thus, the heterologous expression system for actinoallolide biosynthetic gene cluster was established and it could be used for genetic modification of the gene cluster to synthesis new actinoallolide analogs.

Free Research Field

微生物薬品化学