Objective　To　increase　the　production　of　(R)-alpha-lipoic　acid　directly　from　octanoic　acid　using　engineered　Escherichia　coli　with　the　regeneration　of　S-adenosylmethionine.Results　The　biosynthesis　of　(R)-alpha-lipoic　acid　(LA)　in　E.　coli　BL21(DE3)　is　improved　by　co-expression　of　lipoate-protein　ligase　A　(LplA)　from　E.　coli　MG1655　and　lipoate　synthase　(LipA)　from　Vibrio　vulnificus.　The　engineered　strain　produces　20.99　mu　g　l(-1)　of　LA　in　shake　flask　cultures.　The　titers　of　LA　are　increased　to　169.28　mu　g　l(-1)　after　the　optimization　of　the　medium　components　and　fermentation　conditions.　We　find　that　the　[4Fe-4S]　cluster　is　important　for　the　activity　of　LipA　and　co-expression　of　iscSUA　promotes　the　regeneration　of　the　[4Fe-4S]　cluster　and　leads　to　the　highest　LA　titer　of　589.30　mu　g　l(-1).Conclusion　The　method　described　here　can　be　widely　applied　for　the　biosynthesis　of　(R)-alpha-lipoic　acid　and　other　metabolites.