**4. Conclusions**

Our work provides some relevant findings. First, we demonstrated that fungi are able to perform different biotransformations on the isomeric forms of the C13 apocarotenoids ionone, theaspirane and damascone. With respect to the eleven strains tested, we observed that the most common chemical transformations are oxidation reactions that afford oxygenated products such as hydroxy- keto- or epoxy-derivatives. On the contrary, the reduction of the keto groups or the reduction of the double bond functional groups are less relevant transformations, occurring for few substrates and yielding a minority amount of products.

A very significant feature of our study concern the prospective applicability of the fungi-mediated biotransformation of apocarotenoids for the synthesis of high value natural flavours. Since some ionone, damascone and theaspirane isomers are available in natural form and the biotransformation of a natural precursor is considered a 'natural method' of synthesis, the flavours obtained by means of the fungi-mediated reactions described above possess the natural status and could be commercialized accordingly.

Finally, we would like to highlight that our microbial biotransformations allow the preparation of many derivatives whose synthesis, using the classical chemical reactions, is very difficult. For example, different fungal strains proved to be able to oxidize some inactivated positions of the ionone or theaspirane framework, such as the position 2 and 3 of the β- and γ-ionone and the methine carbon linked to the theaspirane oxygen atom. By means of these microbial capabilities, we isolated one new compound (compound **36**) and we devised a new biocatalytic procedure for the synthesis of 2-hydroxy-γ-ionone, 3-hydroxy-γ-ionone, 3,4-dihydroxy-β-ionone and 2,6,10,10 tetramethyl-1-oxa-spiro[4.5]dec-6-ene-2,8-diol (identified as its monoacetate **34**), which are natural apocarotenoids or their direct precursors.

**Supplementary Materials:** The Supplementary Materials are available online.

**Author Contributions:** S.S. and D.D.S. equally contributed to the conceptualization of this study. S.S. and D.D.S. equally contributed to conceive, design and perform the experiments as well as to analyze the data. S.S. wrote the paper.

**Funding:** This research was funded by [Cariplo Fundation] grant number [2014-0568 INBOX (Innovative Biocatalytic Oxidations)].

**Acknowledgments:** The authors thank Cariplo Foundation for supporting this study.

**Conflicts of Interest:** The authors declare no conflict of interest.
