Structure determination and biosynthesis of the antifungal butyrolactols from Streptomyces sp.

Marine actinomycetes have been drawing attention as prolific sources of new bioactive secondary metabolites [1]. In our research for new bioactive secondary metabolites form marine microorganisms, we selectively isolated actinomycete strains from marine sediment samples from the western area of Jeju Island in Republic of Korea and screened their secondary metabolites profiles by LC/MS. During the chemical profile analysis, we observed that one of the actinomycete strains named TH11 (Streptomyces sp.) produces previously reported antifungal butyrolactols A and B, which bear a seven consecutive 1,2-diol moiety [2], and their new derivatives, butyrolactols C and D. Because the absolute configuration of butyrolactol A has not previously determined, we established the stereochemistry of butyrolactol A by J-based configuration analysis using ROESY and HETLOC data and Mosher's method. Biosynthetically interestingly, four oxygen-bearing carbons are missing between the 5-membered lactone ring and the chain with a tertiary butyl group in butyrolactol C compared to butyrolactol A.

The full genome analysis of the producer enabled us to identify the biosynthetic gene cluster of the butyrolactols. Further analysis indicated that the t-butyl starting unit could be originated from valine catalysed by an AdoCbl-dependent isomerase [3] and polyol groups could be synthesized with glycolate extender units. Variation of the chain lengths in butyrolactols A-D will be discussed.

Fig. 1: Relative configuration of Butyrolactol A

Acknowledgements: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (Ministry of ICT and Future Planning) (2014R1A2A1A11053477) and a grant Marine Biotechnology Program (Genome Analysis of Marine Organisms and Development of Functional Applications, PJT200620) funded by Ministry of Oceans and Fisheries, Korea.

Keywords: Butyrolactol, structure determination, microbial secondary metabolite, biosynthesis.

References:

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[2] Kotake C, Yamasaki T, Moriyama T, Shinoda M, Komiyama N, Furumai T, Konishi M, Oki T. Butyrolactol A and, B new antifungal antibiotics taxonomy, isolation, physici-chemical properties, structure and biological activity. J Antibiot 1992; 45: 1442 – 1450

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