01887nas a2200205   4500008004100000022001400041245017700055210006900232260000900301300001600310490000700326520107800333100001901411700001901430700004001449700001901489700002101508700002101529856013101550       2026                        eng d  a2470-134300aEngineering pichia pastoris as a heterologous platform for non-ribosomal peptide biosynthesis of the β-lactam intermediate δ-(L-α-Aminoadipyl)-L-cysteinyl-D-valine (ACV)0 aEngineering pichia pastoris as a heterologous platform for nonri  cJUN   a32038-320480 v113 a<p>
	The production of nonribosomal peptides (NRPs) in non-native hosts remains challenging due to the size and complexity of the biosynthetic enzymes. Here, we report the first successful reconstruction of the delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) pathway in Pichia pastoris. By introducing codon-optimized versions of the pcbAB and npgA genes directly into the genome, we were able to rebuild the minimal pathway required for ACV synthesis, which we confirmed using LC-MS/MS. Although the starting strain produced only small amounts of ACV (similar to 5 ng/mL), yields increased 10-fold after adaptive evolution (similar to 50 ng/mL) and further improved with precursor supplementation (similar to 60 ng/mL). Transcriptomic analysis showed that the engineered strain reorganized its metabolism to meet the energy and precursor demands of NRPS activity. Overall, this study suggests that P. pastoris can serve as a practical, proof-of-concept host for complex NRP biosynthesis and lays the groundwork for future engineering of beta-lactam pathways.</p>
1 aJogi, Shraddha1 aJagtap, Rutuja1 aSubrahmanyam, Yalamanchili, Venkata1 aSharma, Monika1 aKulkarni, Mahesh1 aRaghunathan, Anu  uhttps://library.ncl.res.in/content/engineering-pichia-pastoris-heterologous-platform-non-ribosomal-peptide-biosynthesis-%CE%B2