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Pteridic acids F and H (PTA-F and PTA-H), originally isolated from\n                      <jats:italic>Streptomyces iranensis<\/jats:italic>\n                      HM 35, are plant growth\u2013promoting polyketides with reported activity under drought and salinity stress. However, reported production was extremely low (~\u20090.08 and 0.02\u00a0mg\/L), limiting further development and application. Here, we established a heterologous production platform for PTA biosynthesis by cloning the 68-kb type I polyketide synthase biosynthetic gene cluster using Cas12a-assisted precise targeted cloning using in vivo Cre-lox recombination (CAPTURE), followed by CRISPR-Cas9-mediated genomic integration and promoter engineering in\n                      <jats:italic>Streptomyces<\/jats:italic>\n                      hosts. Initial heterologous expression resulted in detectable elaiophylin production but not PTA, whereas BGC engineering with the strong constitutive\n                      <jats:italic>kasO<\/jats:italic>\n                      p* promoter enabled PTA production (although\u00a0below\u00a0the limit of quantification). Genome-scale metabolic model\u2013guided media optimization further improved production and fed-batch fermentation yielded 1.7\u00a0mg\/L PTA in J1074-PTA-\n                      <jats:italic>kasO<\/jats:italic>\n                      p* and 2.8\u00a0mg\/L PTA in NBC1270-PTA-\n                      <jats:italic>kasO<\/jats:italic>\n                      p*. These titers represent a\u00a0more tha n 20-fold increase compared with the native producer under comparable conditions. This work provides the first functional heterologous platform for PTA biosynthesis and demonstrates how synthetic biology and genome-scale metabolic modeling can be combined to improve production of complex plant-beneficial polyketides.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Direct BGC cloning and engineering enabled production of PTA in heterologous host.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Genome-scale metabolic models (GEMs) guided media optimization for PTA production.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Fed-batch fermentation achieved<\/jats:italic>\n                      \u2009&gt;\u2009\n                      <jats:italic>20-fold PTA titer improvement over native strain.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-026-13915-w","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T06:25:39Z","timestamp":1781936739000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterologous production of a plant biostimulant in Streptomyces albidoflavus"],"prefix":"10.1007","volume":"110","author":[{"given":"Renata","family":"Sigrist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Te","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta Revent\u00f3s","family":"Montan\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gockel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijun","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"J\u00f6nsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilmann","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emre","family":"\u00d6zdemir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"13915_CR1","doi-asserted-by":"publisher","first-page":"101955","DOI":"10.1016\/j.xpro.2022.101955","volume":"4","author":"M Alvarez-Arevalo","year":"2023","unstructured":"Alvarez-Arevalo M, Sterndorff EB, Faurdal D, J\u00f8rgensen TS, Mourched A-S, Vuksanovic O, Saha S, Weber T (2023) Extraction and Oxford Nanopore sequencing of genomic DNA from filamentous Actinobacteria. 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