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Farnesol is a secreted autoregulatory molecule that represses filamentation. It is derived from farnesyl pyrophosphate (FPP), an ergosterol biosynthesis pathway intermediate. Although Dpp1, Dpp2, and Dpp3 were proposed to synthesize farnesol, a mutant lacking all three had only a modest reduction in farnesol. To identify other farnesol biosynthesis genes, we employed transcription factor mutants that underproduced or overproduced farnesol in a screen and analyzed their transcriptomes.\n                      <jats:italic toggle=\"yes\">CWH8<\/jats:italic>\n                      was the only transcript correlated with farnesol production. Cwh8 is a lipid phosphatase known to recycle dolichyl pyrophosphate during glycosylation of cell wall proteins. The\n                      <jats:italic toggle=\"yes\">cwh8\u0394\u0394<\/jats:italic>\n                      mutant had a &gt; 99% reduction in farnesol compared to the parent strain and was hyperfilamentous in embedded conditions. It had ~900 fold lower levels of farnesyl phosphate, the product of FPP dephosphorylation, suggesting Cwh8 acts directly on FPP. Complementation of the\n                      <jats:italic toggle=\"yes\">C. albicans cwh8\u0394\u0394<\/jats:italic>\n                      mutant with\n                      <jats:italic toggle=\"yes\">CWH8<\/jats:italic>\n                      from\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      restored cell wall integrity and farnesol production. However, complementation with\n                      <jats:italic toggle=\"yes\">CWH8<\/jats:italic>\n                      from\n                      <jats:italic toggle=\"yes\">Clavispora lusitaniae<\/jats:italic>\n                      , a species lacking farnesol signaling, restored cell wall integrity but failed to rescue farnesol production. This indicates that while Cwh8\u2019s role in maintaining cell wall integrity is conserved, differences in substrate specificity or interactions with species-specific cofactors underlie its involvement in farnesol biosynthesis in\n                      <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                      . Finally, fluconazole was fungicidal for\n                      <jats:italic toggle=\"yes\">cwh8\u0394\u0394<\/jats:italic>\n                      rather than fungistatic. These studies demonstrate how an extracellular signaling system can arise and be co-opted to promote fungal fitness in complex environments.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Farnesol secretion distinguishes the human opportunistic pathogen\n                        <jats:italic toggle=\"yes\">Candida albicans<\/jats:italic>\n                        from non-secreting, non-pathogenic yeasts. Despite 20 years of research, surprisingly little is known about how farnesol is synthesized and regulated. Using transcriptomic profiles from mutants with altered farnesol production, we identified\n                        <jats:italic toggle=\"yes\">CWH8<\/jats:italic>\n                        as a critical enzyme in this process.\n                        <jats:italic toggle=\"yes\">CWH8<\/jats:italic>\n                        null mutants produced no farnesol. Our novel assay measuring cellular farnesyl pyrophosphate (FPP) and farnesyl phosphate (FP) showed that Cwh8 converts FPP to FP in the first step of farnesol biosynthesis, in addition to its established role in recycling dolichyl pyrophosphate. Farnesol-secreting fungi had huge metabolic pools of FP, while nonsecretors had small pools. Furthermore, expressing\n                        <jats:italic toggle=\"yes\">CWH8<\/jats:italic>\n                        from\n                        <jats:italic toggle=\"yes\">Clavispora lusitaniae<\/jats:italic>\n                        , a non-farnesol-secreting species, failed to restore farnesol production in\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        . This suggests that changes in Cwh8 enzyme specificity drove the evolution of farnesol as a signaling molecule and virulence factor in\n                        <jats:italic toggle=\"yes\">C. albicans<\/jats:italic>\n                        .\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02290-25","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T12:00:29Z","timestamp":1757332829000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Cwh8 moonlights as a farnesyl pyrophosphate phosphatase and is essential for farnesol biosynthesis in\n                    <i>Candida albicans<\/i>"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-4826","authenticated-orcid":true,"given":"Daniel J.","family":"Gutzmann","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/043mer456","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences, University of Nebraska-Lincoln","place":["Lincoln, USA"]},{"id":[{"id":"https:\/\/ror.org\/049s0rh22","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth","place":["Hanover, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory H. 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