Gram-positive bacteria of the genus Streptomyces are industrially important microorganisms, producing >70% of commercially important antibiotics. The production of these compounds is often regulated by low-molecular-weight bacterial hormones called autoregulators. Although 60% of Streptomyces strains may use γ-butyrolactone–type molecules as autoregulators and some use furan-type molecules, little is known about the signaling molecules used to regulate antibiotic production in many other members of this genus. Here, we purified a signaling molecule (avenolide) from Streptomyces avermitilis —the producer of the important anthelmintic agent avermectin with annual world sales of $850 million—and determined its structure, including stereochemistry, by spectroscopic analysis and chemical synthesis as (4 S ,10 R )-10-hydroxy-10-methyl-9-oxo-dodec-2-en-1,4-olide, a class of Streptomyces autoregulator. Avenolide is essential for eliciting avermectin production and is effective at nanomolar concentrations with a minimum effective concentration of 4 nM. The aco gene of S. avermitilis, which encodes an acyl-CoA oxidase, is required for avenolide biosynthesis, and homologs are also present in Streptomyces fradiae , Streptomyces ghanaensis , and Streptomyces griseoauranticus , suggesting that butenolide-type autoregulators may represent a widespread and another class of Streptomyces autoregulator involved in regulating antibiotic production.

The first total synthesis of extracellular factor, ''Avenolide'', in Streptomyces avermitilis has been achieved using a convergent approach. The stereogenic centers in two key segments were installed using Sharpless epoxidation and dihydroxylation. This synthetic study allowed the determination of the absolute configuration of avenolide as 4S,10R, and yielded important information on its structure-activity relationship.

Total Synthesis and Absolute Configuration of Avenolide, Extracellular Factor in Streptomyces avermitilis. -(4S,10R)-Avenolide (I), its (4S,10S)-isomer and 10-deoxy avenolide are synthesized. The structure-activity relationships are studied. -(UCHIDA, M.; TAKAMATSU, S.; ARIMA, S.; MIYAMOTO, K. T.; KITANI, S.; NIHIRA, T.; IKEDA*, H.; NAGAMITSU, T.; J. Antibiot. 64 (2011) 12, 781-787, http://dx.doi.org/10.1038/ja.2011.90 ; Kitasato Inst. Life Sci., Kitasato Univ., Kanagawa 228, Japan; Eng.) -R. Langenstrassen 17-209

The authors of the above article noted an error in publication of this paper. In the experimental section, present on page 787, the optical rotation of (4S,10R)-avenolide (1)