Abstract
In our effort to find the key intermediates of lankacidin biosynthesis in Streptomyces rochei, three UV-active compounds were isolated from mutant FS18, a gene disruptant of lkcA encoding a non-ribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) hybrid enzyme. Their structures were elucidated on the basis of spectroscopic data of NMR and MS. Two compounds of a higher mobile spot on silica gel TLC (Rf=0.45 in CHCl3-MeOH=20:1) were determined to be an epimeric mixture of citreodiol and epi-citreodiol at the C-6 position in the ratio of 2:1. In contrast, the compound of a lower mobile spot (Rf=~0 in CHCl3-MeOH=20:1) was identical to a 28-membered polyene macrolide pentamycin. The yields of citreodiols and pentamycin in FS18 were 5- and 250-fold higher compared with the parent strain. Introduction of a second mutation of srrX, coding a biosynthetic gene of the signaling molecules SRBs, into mutant FS18 did not affect the production of three metabolites. Thus, their production was not regulated by the SRB signaling molecules in contrast to lankacidin or lankamycin.
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Acknowledgements
We thank Professor John C. Vederas (University of Alberta) for a kind gift of natural pentamycin. We thank Mrs. Tomoko Amimoto (Natural Science Center for Basic Research and Development, Hiroshima University) for the measurement of high-resolution mass spectra. This work was supported by a Grants-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT), and a Charitable Trust Araki Medical and Biochemical Research Memorial Fund.
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Cao, Z., Yoshida, R., Kinashi, H. et al. Blockage of the early step of lankacidin biosynthesis caused a large production of pentamycin, citreodiol and epi-citreodiol in Streptomyces rochei. J Antibiot 68, 328–333 (2015). https://doi.org/10.1038/ja.2014.160
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DOI: https://doi.org/10.1038/ja.2014.160
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